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A route to optically active variously substituted 4-methyl- and 4-methyl-7-substituted 1,3,4,5-tetrahydro-2H-1,5-benzo-diazepin-2-ones as analogues of commercially available Lofendazam (7-chloro-5-phenyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one, 1) was developed. Fortyone variously substituted optically active compounds having the same configuration were prepared and the UV and CD spectra of the parent compounds bearing no additional substitution in the benzene ring are discussed.

Syntheses of 5α-cholesteno[3,2-d]- (5a), [2,3-d]- (12a), and [3,4-d]pyrimidines (15a) have been achieved by using hydroxymethylene derivatives of relevant cholestanones prepared from cholesterol (1). Their CD spectra exhibit at least three Cotton effects between 300 to 200 nm, a first CD band around 290, a second one around 260 and a third one around 220 nm. A quadrant rule is developed and applied to the determination of the sign of the first CD band, while a helicity rule is applicable to the third CD band. The first band is positive in the [3,2-d] series, whereas it is negative in the [2,3-d] and the [3,4-d] series. The third band is negative in all three series.

The correlation between the absolute configuration and CD of aza- and thiaflavanone (1, 2) is discussed: the 2R configuration for the laevorotatory enantiomers has been established by a comparison of their CD data with those of (S)-(−)-3. For the Cotton effect within the n π* band of 1 and 2 the same helicity rule is valid as for the homochirally analogous flavanones (3). Starting from (S)-(−)-flavanone (3) and cholesterol (5), we have synthesized the chromane derivatives 4 and 20, respectively. The 1Lb band of the chromane chromophore has been unequivocally identified in the range between 255 and 290 nm in the CD spectra of 4 and 20. For this Cotton effect the opposite helicity rule is valid as compared with the homochirally analogous tetralins: the P/M helicity of the hetero ring leads to a negative/positive CD within the 1Lb band. The modification of the helicity rule can be explained with the help of Petruska's “q values”.

Synthesis of unsubstituted 5X'-cholesteno(3,2-d)- (5), (2,3-d)- (12), (3,4-d)(15) and 5.C- and 5 ~-cholest-3-eno(4,3-d)pyrimidines (21) and (21') has been achieved using hydroxymethylene derivatives of relevant cholestanones prepared from cholesterol(1). Their 2'-derivatives (5a - Se), (12a), (15a - 15c), (21a - 21c) and (21'a,21'b) could also be prepared. Attempts to prepare cholest-l-eno(l,2-d)pyrimdine system through 5X-cholestan-l-one(28) failed. 5 $-Cholest-6-eno(7,6-d)pyrimidine(33) was prepared by the reaction of cholestan-7-one with trisformylaminomethane. Three Cotton effects were observed between 350-200 nm in all these compounds intheir CD spectra. They have been assigned to n 3 K* and 7T -tT*transitions from long to short wave lengths. Quadrant rule has been applied for determining the sign of the first band CD, while helicity rule has been applied for the third band CD. Present work describes the synthesis of six series of optically active cholestenopyrimidines (Fig.l), e.g. 5 and its 2'-derivatives (5a-5e), 12 and its

Synthesis of Medium and Large Rings, XXXIII[1].–Optically Active 3a,6-Methanohydroazulenes via Chiral Induction of the Solid-State Photochemical Rearrangement of Bis(1,2:5,6-di-O-isopropylidene-α-D- and -α-L-glucofuranos-3-O-yl) 3,6-Hexanooxepine-4,5-dicarboxylate Irradiation of an aqueous suspension of the crystalline 3,6-hexanooxepine-4,5-dicarboxylic esters 2a and 2b affords the (3aS,6R,8aR)- and (3aR,6S,8aS)-methanohydroazulenes 3a and 4b in 54–58% yield with 92–93% de. Irradiation of an ethereal solution of 2a–2d on the other hand proceeds with low diastereoselectivity. The absolute configurations were established by X-ray structural analysis of the dimenthyl ester (+)-3d, comparison of CD spectra and chemical transformations. The origin of the high diastereoselectivity of the rearrangements 2a 3a and 2b 4b in the solid state is discussed on the basis of the X-ray structural analysis of the 3,6-heptanooxepine (–)-5a. Procedures for the removal of the chiral auxiliaries are described. Di-O-isopropylidene-α-L-glucofuranose is recycled in 95% yield.

Asymmetric reactions on chiral bis (diphenylphosphine) metal complexes having C2 symmetry axis of the chelate ring obey the simple stereochemical rules which establish a relationship between the product configuration and complex conformation. The stereochemical basis of the application of this rule has been studied on the example of the cross-coupling reaction of crotyl alcohol derivatives and arylmegnesiumbromides on trans-bis-1S,2S- and trans-bis-1R,2R- (diphenylphosphino)cyclopentanenickel dibromide (NiBr2 ((SS)-dpcp) and NiBr2 ((RR)-dpcp)). Monitoring the reaction mixture by circular dichroism and 31P NMR spectroscopy shows that this reaction goes through Ni(Ph)Br(dpcp), NiPh2(dpcp) and Ni0(dpcp) intermediates. 31P NMR spectroscopy, just as CD, did not reveal the π-allyl (Y)Ni(dpcp) species (Y = leaving group of the crotyls). Probably, they take part in the reaction at a very small concentration. The observed effect of the influence of Y volume on the enantiomeric excess value of the reation was explained on the assumption of an equilibrium between two forms: in the one, the Ni in Ni(Y) (dpcp) is coordinated to the crotyl function, and in the other, Y is covalently bonded to the crotyl, with the Ni π-bonded to the crotyl double bond. Exchange of phenyl for 1-naphthyl group in ArMgBr is accompanied by a decrease of ee from 58% to 0%. Loss of enantioselectivity can be explained by attack of the bulky nucleophile from outside but not within the inner sphere of the complex as in the case of Ph. Major and minor diastereomers (8:1) of π-allyl(1-Np)Ni((SS)-dpcp) are not intermediates of this reaction but deadlock substances.

Chiroptical properties of the title compounds have been studied. The influence of the substitution pattern of the aromatic moiety and the consequence of the amide → thioamide conversion are discussed as well.

Bidentate complexes of dimolybdenum tetraacetate with 1,3-diaxial diols show Cotton effects around 490–540 nm (CD band I), 400–440 nm (II), 350–380 nm (III), 320 nm (IV) and 280 nm (V). The sign of the Cotton effect II can be predicted by a proposed sector rule. It seems that from the Cotton effects for cyclic 1,3-diols the absolute configurations or conformations can be obtained.

3-Hexulose phosphate synthase catalyzes the aldol reactions between D-ribulose 5-phosphate 1 and a rather wide range of aldehydes. The stereoselectivity of the reaction was investigated with propionaldehyde 3 as substrate. The sense of chirality at carbon atom 5 is definite, but two isomers at carbon atom 6 are formed during formation of the new CC bond.

From forty one chiral benzodiazepin-2-ones the UV and CD data are reported and the bands discussed with respect to corresponding electronic transitions respectively stereochemical features.

Hydrolysis of 3β-5-diacetoxy-5β-cholestan-6-one oxime (1) gave seven products which, in addition to 3β-acetoxy- and (6E)-3β-hydroxy-5-methoxy-5α-cholestan-6-one oxime (3 and 4), are identified as the dimeric steroids (6E,6′E)-6-(6′-hydroxyimino-5′α-cholestan-5′-yl-oximino)cholestanes 6–10. On the other hand, the 3α epimer 3α,5-diacetoxy-5β-cholestan-6-one oxime (2) afforded the monomeric (6E)-3α-hydroxy-5-methoxy-5α-cholestan-6-one oxime (5) and (6E)-3α-hydroxy-4-cholesten-6-one oxime (11) only. All new compounds are characterized by NMR and MS methods. The CD spectra of 1–12 are documented.

Starting from cholesterol the three possible stereoisomeric 1,4-benzodioxanes 24, 31, 32 and a series of analogues with 2βH,3βH configuration (25–27, 29, 30) have been synthesized. The α band of the 1,4-benzodioxane chrompohore has been unequivocally identified in the CD spectra between 325–300 nm. For its Cotton effect the same helicity rule is valid as for homochirally analogous tetralins: the P/M helicity of the heteroring leads to a positive/negative CD within the α-band. The (2′R,3′R) configuration of 6 has been established by a comparison of its CD data with those of 39 and with the help of the above-mentioned helicity rule. This allows the assignement of the (2S,2′R,3′R) configuration of (−)-silandrin (3).

3-Hexulose phosphate synthase catalyzes the aldol reactions between D-ribulose 5-phosphate 1 and a rather wide range of aldehydes. The stereoselectivity of the reaction was investigated with propionaldehyde 3 as substrate. The sense of chirality at carbon atom 5 is definite, but two isomers at carbon atom 6 are formed during formation of the new CC bond.

Revision of previous work shows that PLE-cataiyzed hydrolysis of 1 leads to the (S)-alcohol 5 and not the (R)-alcohol 3 . However the homologue 2 gives the (R)-alcohol 4 .

The CD spectra Of some resorcylic acid macrocyclic lactones (RAL) are reported. The spectra Of the E,Z -isomeric ketones 1,6 are very similar in shape and magnitude. The Cotton effects Of the 7α-alcohols 2 and 7 are also Of the same shape, but the Δϵ values Of 7 are Only ca. 50% Of those Of the Others. The E-7β-Ol 3 gives a completely different CD, whereas in the Z-series 8 shows a similar CD curve as 6 and 7 , but with again reduced magnitude. The CDs Of the acetates 4 and 5 are very similar to those Of the corresponding alcohols 2 and 3 , resp. The effect Of the 7a- and 7β-hydroxy Or acetoxy group On the absolute conformation Of the “chain” from C(5) to C(10) is thus transmitted to the absolute value of the torsional angle Of the inherently chiral chromophore C(11)-C(12)-C(12a)-C(1a)-C(=0)O in 2,3 and 4,5 , resp. The CD spectra Of the E,Z -isomers do not exhibit straightforward correlation with the configuration around the C=C double bond.

Some oximes and oxime acetates of transoidal cholestenones have been synthesized. In three cases of stable syn/anti pairs of oximes both stereoisomers could be separated. The CD-spectra of all compounds have been measured. All syn-isomers show an additional CD band around 280 nm, which does not exist for anti-oximes.

The four possible diastereomeric 5,7-oxido-6-hydroxyiminocholestanes and their O-acetates have been synthesized. The stereochemistry of one of the latter has been proved unequivocally by x-ray diffraction. Their 1H and 13C NMR and also their circular dichroism spectra are discussed. It is now also possible to determine unequivocally the stereochemistry of the ring-junction geometry and the oxime E or Z stereochemistry.

Chiroptical properties of the title compounds have been studied. The influence of the substitution pattern of the aromatic ring and the configuration of the centre of chirality on the Cotton effects appearing in various wavelengths ranges are discussed.

Treatment of 2- O -benzoyl ( 1 ) and 2- O -acetyl ( 5 ) derivatives of benzyl 4,6- O -benzylidene-3- O -(2,3,4-tri- O -acetyl-α- l -rhamnopyranosyl)-β- d -galactopyranoside under Zemplen conditions (catalytic amount of sodium methoxide in methanol) gave partially deacylated disaccharides in which the 2- O -acyl groups were retained. Likewise, a similar result was obtained with the β- l -rhamnopyranosyl analogue ( 3 ) of 1 . This anomalous reaction was used in a synthesis of the title trisaccharide ( 17 ) and of methyl 4,6- O -benzylidene-3- O -(2,3:4,6-di- O -isopropylidene-α- d -mannopyranosyl)-α- d -glucopyranoside, an intermediate for the synthesis of 2- O -glycosyl-3- O -(α- d -mannopyranosyl)- d -glucoses.

Some oximes of 4- and 6-ketosteroids, of des-A-5-keto-steroids, and the related compounds 31 and 33 have been synthesized. In three cases stable B / Z pairs are formed which could be separated. The CD-spectra of all compounds have been measured. The Cotton effects around 217 run of the 6-hydroxyimino-5α-steroids (1 – 18, 34, 36) are negative, those of the corresponding 4-analogues (20 – 23) are positive. A similar relationship holds for the des-A-steroidoximes 24 – 26 vs. 27, and the syn-oximes 34/36 vs. their anti-analogues 35/37. This Cotton effect can, therefore, be used for the determination of the configuration of such oximes. The Cotton effects below 200 nm do not always show similar regularities.

Cholesteno Indoles, I. – Preparation of 1′H-5α-Cholest-2-eno[3,2-b]indoles 1′H-5α-Cholest-2-eno[3,2-b]indole (1a), the corresponding N-methyl, N-acetyl, and N-formyl compounds 1b–d, as well as the respective methoxy derivatives 2b–5d have been synthesized as model compounds for intended CD investigations. Application of the Fischer indole synthesis afforded the compouds 1a–5a which were N-methylated to 1b–5b, N-acetylated to 1c–5c, and N-formylated to 1d–5d.

The first CD spectra of optically active ferricinium salts are reported. Cotton effects corresponding to the metal-ligand charge-transfer band have been observed for the compound with planar chirality.

The CD of ketoximes of defined (E)/(Z configuration and some of their O-derivatives of steroids (4-en-3-ones, 4-en-6-ones, 5-en-7-ones, 4,6-dien-3-ones) and monoterpenoids (verbenone, carvone) have been investigated. All show two Cotton effects around 250 nm (band II) and 230 nm (band III), which usually have opposite signs. For the first-mentioned one a rule is proposed for the correlation between CD and absolute configuration. Most of the (Z)-oxime derivatives give an additional Cotton effect around 290 nm (band I), whose sign is always opposite to that of band II.

Synthesis of Medium and Large Rings, XXVII1. - Chromatographic Separation of the Enantiomeric 3.6-Heptanophthalides. - A Contribution to the Problem of the Absolute Configuration of [nJ Paracyclophanecarboxylic Acids The partial chromatographic separation of the racemic title compound 1 (ee = 40%) was achieved on triacetylcellulose with ethanol using a recycling technique. Comparison of the CD spectra of (+)22365-1 with (+)22365-2 leads to the absolute configuration (P) for both compounds. This assignment is of interest in view of earlier configurational assignments for [n]paracyclophanecarboxylic acids.

The 1 B 2u -band CD of siccanin ( 3 ) and some of its derivatives obeys the known rules for the benzene chromophore with the appropriate substitution pattern. The CD spectrum of the chromanone 8 is better resolved than that of related flavanones, the band between 300–320 nm is most probably the 1 B 2u -band of this chromophore. The non-planar styrenes 10–12 symmetrically substituted in the benzene ring with respect to the “pivot” bond follow Crabbe's rule, and the absolute configuration of siccanochromene-A ( 13 ) in the chromene ring follows from its CD to be S .

Die aus (Acyl)(aryl)aminen zuganglichen Gemische ihrer O- und N-Trimethylsilyl-Derivate ergeben unter Trifluormethansulfonsaure-trimethylsilylester-Katalyse mit den Peracetaten von β-D-Glucopyranose oder β-D-Glucopyranuronsaure-methylester die entsprechenden β-D-N-(Acyl)-(aryl)-N-glycoside. Unter den Reaktionsbedingungen wird das sich allein umsetzende O-TMS-Derivat laufend aus seinem N-TMS-Isomeren nachgebildet, die Ausbeuten sind daher meist sehr gut. Das N-(p-Anisyl)amid 4 ergibt ausschlieslich das N-TMS-Derivat und reagiert daher nicht zum N-Glycosid. Selektive Entacetylierung am Stickstoff gelingt mit Triethyloxonium-fluoroborat/NaHCO3, Verseifung aller O-Estergruppen mit Natriummethanolat. On a New Synthesis of N-Aryl-N-glucosides and N-Aryl-N-glucosiduronic Acid Methyl Esters Mixtures of O- and N-trimethylsilyl derivatives obtainable from (acyl)(aryl)amines give with the peracetates of β-D-glucopyranose or methyl β-D-glucopyranuronate, respectively, under catalysis with trimethylsilyl trifluoromethanesulfonate the corresponding β-D-N-(acyl)(aryl)-N-glycosides. Under these conditions the exclusively reacting O-TMS derivative is continuously generated from its N-TMS isomer, the yields are, therefore, mostly very high. The N-(p-anisyl)amine 4 affords solely the N-TMS derivative and thus does not react to give its N-glycoside. Selective deacetylation at the N atom is achieved with triethyloxonium fluoroborate/NaHCO3, saponification of all O-esters with sodium methanolate.

(+)- and (−)-1 (N,N,N′,N′-Tetramethyldithiooxamide) were enriched by semipreparative liquid chromatography on triacetylcellulose. According to1HNMR in the presence of an optically active auxiliary, the sample of (+)365-1 had an enantiomeric purity of 0,50±0,01, thus permitting to calculate the CD spectrum for the pure enantiomer. The CD and UV spectra are discussed in terms of qualitative MO theory. Thereby, the absolute configuration of (+)365-1 is determined to be (R).

Resume Die zwei Phenylchromophore eines optisch aktiven 1,2-disubstituierten 1,2-Diphenylethans geben unabhangig voneinander Cotton-Effekte innerhalb des Wellenlangenbereichs der α-Bande. Durch Bildung der Summen-und Differenz-CD-Kurve fur ein threo/erythro Paar erhalt man CD-Spektren, die fur jedes “Halbmolekul” charakteristisch sind, und die im allgemeinen zwei 0-0—Linien um 37230 cm -1 aufweisen. Aus deren Vorzeichen kann die absolute Konfiguration an jedem der Chiralitatszentren eindeutig bestimmt werden.

The syntheses of two new ring systems, 5α-cholest-2-eno[3,2-e]-(6) and 5α-cholest-2-eno[2,3-e]-as-triazine (11) are described. While the reaction of diketone 1 with semicarbazide hydrochloride results selectively in derivatives of 6, S-methylisothiosemicarbazide under basic conditions affords the other possible ring closure product 11. An unequivocal decision between both types was made by X-ray analysis of compound 9. Comparison of the UV and CD spectra shows that besides the two absorptions appearing in the UV spectra additional ones can be observed in the CD, which may be assigned to further n – π* or only slightly allowed π – π* transitions. Synthese, Rontgen-Strukturanalyse und CD von Cholesteno-as-triazinen1) Die Synthesen von zwei neuen Ringsystemen, 5α-Cholest-2-eno[3,2-e]- (6) und 5α-Cholest-2-eno[2,3-e]-as-triazin (11) werden beschrieben. Wahrend das Diketon 1 mit Semicarbazid-hydrochlorid selektiv zu Derivaten von 6 reagiert, ergibt S-Methylisothiosemicarbazid das andere mogliche Ringschlusprodukt 11 unter basischen Reaktionsbedingungen. Zwischen den beiden Typen konnte mit Hilfe einer Rontgen-Strukturanalyse von 9 unterschieden werden. Vergleich der UV- und CD-Spektren zeigt, das auser den zwei Absorptionen, die im UV-Spektrum auftreten, zwei andere in den CD-Spektren beobachtet werden, die weiteren n – π*- oder nur wenig erlaubten π – π*-Ubergangen zugeordnet werden konnen.

The complexes of formula [CuSu 2 Am 2 * ] formed in situ from amino steroids (Am * ) and a methylene chloride solution of the complex [CuSu 2 Pr 2 ] (Su: succinimidate; Pr: isopropyl amine) show in the range of the d-d bands two Cotton effects at approx. 700 (Band I) and 600 nm (Band II), whose signs are correlated with the preferred torsion angle of the H 2 N-Cu moiety: a positive torsion angle leads to a positive CD-band I and to a negative CD-band II. These complexes form useful Cottonogenic derivatives of primary amino compounds.

Several optically active 1,2-di- and 1,3,5-trisubstituted benzene derivatives have been synthesized, in which one substituent is chiral, the others being methyl, ethyl, or neopentyl. The CD spectra within the α-band can be explained well by making use of Platt and Petruska's q values. While introduction of OH at the benzylic position of a substituent inverts the direction of the corresponding electric transition moment vector in the plane of the ring, this has no such influence upon the magnetic transition moment perpendicular to the ring. Circulardichroismus, XCI: — Synthese und CD von Benzolderivaten mit Mehreren ahnlichen Substituenten Mehrere optisch aktive 1,2-di- und 1,3,5-trisubstituierte Benzolderivate, in denen ein Rest chiral ist, die anderen Methyl, Ethyl oder Neopentyl sind, wurden dargestellt. Die CD-Spektren innerhalb der α-Bande lassen sich unter Verwendung der von Platt und Petruska eingefuhrten q-Werte gut deuten. Wahrend die Ein-fuhrung von OH in benzylischer Position eines Restes zur Richtungsumkehr des zugehorigen elektrischen Ubergangsmoments in der Ringebene fuhrt, hat dies auf das entsprechende magnetische Ubergangsmoments senkrecht zum Ring keinen solchen Einflus.

Eine diastereo- und enantioselektive Synthese des Homoallylalkohols 5 aus dem Boronester 4 eroffnete den Zugang zu optisch aktiven Isomeren des Stegobinons. Stegobinon-Isomere mit der richtigen absoluten Konfiguration an C-2 wurden ausgehend von (3S)-3-Hydroxy-2-methylbuttersaureester 17 dargestellt. Das CD-Spektrum des Isomeren 20B entsprach dem des Naturstoffs. Daraus wurde die konfiguration zu 2S, 3R, 7R fur das naturliche Stegobinon abgeleitet und durch eine Rontgenstrukturanalyse des 7-Epistegobinons (20A) erhartet. Stereoselective Synthesis of Alcohols, IX. Absolute configuration of Stegobinone Diastereoselective as well as enantioselective conversion of the boronate 4 into the homoallyl alcohol 5 served as basis for the synthesis of optically active stegobinone isomers. Material with the correct absolute configuration at C-2 was obtained starting from (3S)-3-hydroxy-2-methyl-butyrate 17. The CD spectrum of the isomer 20B corresponded to that of the natural product. Its Configuration was assigned as 2S, 3R, 7R and was substantiated by an X-ray structure determination of 7-epistegobinone (20A).

Eine allgemein anwendbare Dodekantenregel wurde entwickelt, mit der das Vorzeichen des Cotton-Effektes um 355 nm bei chiralen Xanthogenaten vorausgesagt werden kann. Die Anwendung fuhrt bei uber 30 Saccharid-Xanihogenaten (s. Tabelle) zu befriedigenden Ergebnissen. Die Xanthogenatgruppe nimmt eine bevorzugte Konformation ein, bei der der zum Sauerstoff geminale Ringwasserstoff mit der C = S-Doppelbindung syn-periplanar angeordnet ist. Die Vorzeichen der Dodekantenprojektion wurden anhand von Modellsubstanzen ermittelt. Die von Sjoberg et al.2) angegebene Xanthogenatregel stellt einen Spezialfall der Dodekantenregel dar. Conformational Analysis, XX. A new Dodecant Rule fur Comprehension of the Chiroptical Properties of the Xanthate Chromophore A generally applicable dodecant rule was developed, by which the relative sign of the Cotton effect at 355 nm of chiral xanthates can be predicted. Its application to more than 30 carbohydrate xanthates (see table) gave satisfactory results. In the preferred conformation of the xanthate group the ring hydrogen, in geminal position to the oxygen, adopts a syn-periplanar orientation towards the C = S double bond. The relative signs of the dodecant projections were elucidated by use of model compounds. The rule introduced by Sjoberg et al.2) represents a special case of the dodecant rule.

The conformation and configuration analysis of cis- and trans-furoeremophilanes with hydroxy group in position 9, using 1H NMR and CD spectra, is discussed. Some steroid derivatives were used as models for CD study. A combination of both spectral methods gives complementary results. For natural 9-hydroxyfuroeremophilane the configuration 9β-OH was unequivocally proved and the originally proposed structure of furanopetasin corrected to VII.

Three macrocyclic pyrrolizidine alkaloids have been isolated from the flowers of Crotalaria rosenii . Two of them , madurensine 1 and 7-acetylmadurensine 2 are rare but known alkaloids for which full spectroscopic data have been generated and some erroneous 13 CNMR data in the literature corrected. Crotaflorine 3, an alkaloid previously given a “probable” structure has been subjected to detailed spectroscopic analysis and shown too have structure 3. The recently introduced “COLOC” NMR technique has been used to distinguish between the two alternative structures 1 and 4.

Die Konfigurationsbestimmung der aus den Steroidketonen 1, 6 und 10 hergestellten diastereomeren 2,2-Dialkyl-1,3-oxathiolane gelang mit einer neuen und allgemeinen CD-Sektorregel. — Oxathiolane dieses Types sind bei erhohter Temperatur gegenuber Lithiumtetrahydridoaluminat in Dioxan nicht stabil. Als Zersetzungsprodukte wurden die entsprechenden Alkohole, Ethen und S2- identifiziert. Steroidal 1,3-Oxathioianes; Determination of Configuration by a New General CD Sector Rule, and Their Reduction with Lithium Tetrahydridoaluminate The configuration of the diasteriomeric 2,2-dialkyl-1,3-oxathiolanes prepared from the steroid ketones 1, 6, and 10 was determined using a new and general CD sector rule. — Oxathiolanes of this type are decomposed by lithium tetrahydridoaluminate in dioxane at elevated temperatures. The corresponding alcohols, ethene, and S2- have been identified as decomposition products.

Chromic acid oxidation of manumycin (1), an antibiotic produced by Streptomyces parvulus (strain Tü 64), led to the isolation of 2-(2-methyl-4-oxo-2-pentenoylamino)-5,6-epoxy-1,4-benzoquinone (3) and (-)-(R)-2-methylhexanoic acid (4). From the absolute configuration of 4, determined by comparing its optical rotation with published data, follows the absolute configuration at the center of chirality in the diene side chain of manumycin (1) to be (6'R). Based on the direct comparison of the CD spectra of the two chromic acid oxidation products 2 and 3 with those of the antibiotic G7063-2 (5) and (-)-terreic acid (6) the stereochemistry at C-5 and C-6 of 1 was determined as (5R, 6S). From the negative CD-couplet of manumycin (1) its stereochemistry at C-4 was assigned as (4R).

Diels-Alder-Reaktion von 3,4-Hexamethylenfuran mit Acrylsaure fuhrt mit hoher endo-Selektivitat zur Carbonsaure 1a, die uber ihre α-Phenylethylammonium-Salze in die Enantiomere getrennt wurde. Sowohl der Vergleich der CD-Spektren von (−)-1a und (−)-3 als auch die Rontgenstrukturanalyse des Camphansaureesters 4b legen die 1R,2S,4S-Konfiguration von (−)-1a fest. Ozonolyse des Esters (−)-1b liefert das 2,5-uberbruckte, all-cis- und RSS-Konfigurierte Tetrahydrofuran (−)-5, das sich in 22proz. Ausb. mit Natriummetaperiodat/Kaliumpermanganat zum γ-Lacton (2R,3S)-(−)-6 oxidieren last. Die Hydridreduktion von (−)-6 unter verschiedenen Bedingungen ergibt die optisch aktiven γ-Bislactone (−)-8 und (−)-9 bzw. das Bislactol 10. (−)-8 besitzt die gleiche absolute Konfiguration an allen Chiralitatszentren wie das naturlich vorkommende Bislacton (−)-Canadensolid. Tetrahydrofurans and Lactones, I. - Synthesis and Reactions of Chiral 2,5-Bridged Tetrahydrofurans - A New Approach to Optically Active γ-Lactones and γ-Bislactones Diels-Alder reaction of 3,4-hexamethylenefuran with acrylic acid gives the carboxylic acid 1a with high endo selectivity. 1a was separated into the enantiomers via the α-phenylethylammonium salts. Comparison of the CD spectra of (−)-1a and (−)-3 and the X-ray structural analysis of the camphanoyl derivative (−)-4b lead to the 1R,2S,4S configuration of (−)-1a as well. The 2,5-bridged tetrahydrofuran (−)-5 with all-cis and RSS configuration is obtained by ozonolysis of the ester (−)-1b. (−)-5 can be oxidized to the γ-lactone (2R,3S)-(−)-6 with sodium metaperiodate/potassium permanganate in 22% yield. Hydride reduction of (−)-6 under various conditions leads to the γ-bislactones (−)-8 and (−)-9 or to the bislactol (−)-10. (−)-8 has the same absolute configuration as the naturally occuring (−)-canadensolide.

Die aus Cyclooctin und 3-(Acetoxymethyl)furan in funf Stufen erhaltliche racemische 3,6-Hexanooxepin-4-carbonsaure ((±)-2d) kann mit (+)(R)-1-(1-Naphthyl)ethylamin in die Enantiomeren (+)- und (−)-2d gespalten werden. Ausgehend von (+)- und (−)-2d ist eine stereospezifische Synthese von (+)- und (-)-[6]Paracyclophan-8-carbonsaure ((+)- und (-)-4b) moglich. Schlusselschritte sind dabei die transannulare Bromaddition zu (−)- und (+)-3a und eine anschliesende McMurry-Reaktion. Die Probleme der Interpretation der CD-Spektren des Oxepinesters (+)-2e und der Phancarbonsaure (+)-4b werden eingehend diskutiert. Synthesis of Medium and Large Rings, X. (+)- and (-)-[6]Paracyclophane-8-carboxylic Acid from (+)- and (-)-3,6-Hexanooxepin-4-carboxylic Acid The racemic 3,6-hexanooxepin-4-carboxylic acid ((±)-2d), available in five steps from cyclooctyne and 3-(acetoxymethyl)furan, can be resolved into the enantiomers (+)- and (−)-2d using (+)(R)-1-(1-naphthyl)ethylamine. A stereospecific synthesis of (+)- and (−)-[6]paracyclophane-8-carboxylic acid ((+)- and (−)-4b) is possible from (+)- and (−)-2d as starting materials. Key steps of this synthesis are the transannular addition of bromine to give (−)- and (+)-3a and a subsequent McMurry reaction. The problems involved in the interpretation of the CD-spectra of the oxepin ester (+)-2e and of (+)-4b are discussed in detail.

Internal prodrug analogues of enalapril 1were obtained by reduction of (1S)-N-[1-(ethoxycarbonyl)-3-oxo-3-phenylpropyl]-(S)-alanyl-(S)-proline tert-butyl ester (1) to the alcohols 2a and 2b followed by lactonization to (3S,5S)- and (3S,5R)-N-(tetrahydro-2-oxo-5-phenyl-3-furanyl)-(S)-alanyl-(S)-proline (4a and 4b), both isolated as the maleates. Their configuration and conformation have been elucidated by a combination of 1D- and 2D-NMR techniques and with the help of CD measurements. In vitro inhibition of angiotensin-converting enzyme (ACE) by 4a and 4b has been found to be similar to that of enalapril. Untersuchungen zur Konfiguration und Konformation von 3,5-disubstituierten Dihydro-2(3H)-furanonen Innere Prodrug-Analoge von Enalapril1 wurden synthetisiert: Reduktion von (1 S )- N -[1-(Ethoxycarbonyl)-3-oxo-3-phenylpropyl]-( S )-alanyl-( S )-prolin- tert -butylester ( 1 ) ergab die Alkohole 2a und 2b , deren Lactonisierung lieferte (3 S ,5 S )- und (3 S ,5 R )- N -(Tetrahydro-2-oxo-5-phenyl-3-furanyl-( S )-alanyl-( S )-prolin ( 4a und 4b ), die als Maleat-Salze isoliert wurden. Ihre Konfiguration und Konformation wurden durch eine Kombination von 1D- und 2D-NMR-Techniken, sowie durch CD-Untersuchung aufgeklart. Die in-vitro-Hemmung des „Angiotensin-Converting-Enzyms” (ACE) war bei 4a , 4b ahnlich der bei Enalapril

Die Koenigs-Knorr-Synthese von Glucosiduronsaureestern mit primaren, sekundaren und tertiaren Alkoholen als Glycosidierungskomponenten verlauft mit sehr guten Ausbeuten, wenn Pivaloylreste als Schutzgruppen im Glucosiduronsaureteil benutzt werden. On an Improved Synthesis of β-Glucosiduronic Acid Derivatives The Koenigs-Knorr synthesis of glucosiduronates with primary, secondary, and tertiary alcohols as glycosidation components proceeds with very high yields if pivaloyl rests are used as protecting groups in the glucosiduronic moiety.

Recently Dhar et al. reported the isolation of two new steroidal lactones from the leaves of Datura quercifolia HBK and formulated them as 5α,12α,17α-trihydroxy-1-oxo-6α, 7α-epoxy-22 S -witha-2,24-dienolide and 5α,17α-dihydroxy-1, 12-dioxo-6α,7α-epoxy-22 S -witha-2,24-dienolide on the basis of UV, IR, NMR and MS studies. Further detailed chemical and spectral studies have led to revised structures, namely 5α, 12α-dihydroxy-1-oxo-6α,7α: 24α, 25α-diepoxy-20 S , 22 R -with-2-enolide and 5α-hydroxy-1, 12-dioxo-6α, 7α: 24α, 25α-diepoxy-20 S , 22 R -with-2-enolide, respectively, for the above two compounds.