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The preparation of 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine 2a and 3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine 2b, key intermediates in the synthesis of alpha(V)beta(3) antagonists, is described. The syntheses rely on the efficient double Sonogashira reactions of 2,5-dibromopyridine 3 with acetylenic alcohols 4a/4b and protected propargylamines 10a-e followed by Chichibabin cyclizations of 3,3'-pyridine-2,5-diyldipropan-1-amines 9a/9b.

The major features of the catalytic cycle, including structures of key intermediates, have been determined for the molybdenum-catalyzed asymmetric alkylation. The crystal structure of the π-allyl intermediate exhibits 3-point binding of an anionic ligand. Based on NMR analysis, this species adopts in solution a structure consistent with that observed in the solid state. For the allylic alkylation, the crystal structure predicts the opposite stereochemistry vs. that observed experimentally, which suggests that either the reaction proceeds via a minor isomer (Curtin-Hammett conditions) or with retention of configuration. In addition, CO transfer, promoted by Mo(CO)6, has been found to play a key role in catalyst turnover.

The asymmetric synthesis of 1,3,4-trisubstituted pyrrolidines was accomplished in two steps from readily available starting materials. A 1,3-dipolar cycloaddition of an azomethine ylide to a propiolate ester followed by a Rh-catalyzed asymmetric 1,4-arylation of the resulting pyrroline with an arylboronic acid provided the desired 1,3,4-trisubstituted pyrrolidine products in good to excellent enantioselectivities.

A sensitive gas chromatographic method was developed to monitor the reaction of lithium diisopropylamide (LDA) with dimethyl methylphosphonate (DMMP) to generate the phosphonate carbanion (DMMPA). Analysis of the DMMPA was complicated due to its thermal instability and lack of a chromophore. To overcome these problems, samples were derivatized with trimethylsilylchloride (TMSCl) to form DMMPA–TMS which was sufficiently volatile and thermally stable for GC analysis. Work-up of the derivatized solution with 10 vol.% 2-propanol in hexanes was necessary to quench residual TMSCl prior to GC analysis. The presence of DMMPA–TMS and other sample components was confirmed by GC–MS analysis. This method was utilized to profile the synthesis of DMMPA as DMMP was added to LDA and then aged at −78 °C. Method precision for DMMPA–TMS of less than 0.2% RSD was achieved for repeat injections after normalization of the response with n-dodecane contained in the sample. Due to the thermal instability of the DMMPA, subambient derivatization temperatures were essential to the stability, and consequently, accurate quantification. Under optimized conditions, this derivatization was successfully utilized as a process monitoring tool.

An efficient and practical asymmetric synthesis of (+)-trans-3-hydroxymethyl-4-(3-fluorophenyl)cyclopentanone (1) is described. An asymmetric Mo-catalyzed alkylation reaction was used to establish the first stereocenter and a Cu-catalyzed intramolecular diastereoselective cyclopropanation reaction was used to set the second stereocenter. The last step involved a one-pot ring-opening/deprotection/hydrolysis/decarboxylation sequence that furnished the desired product in good yield.

A simple and scalable method for the preparation of a potentially versatile organostannane, 1-aza-5-chloro-5-stannabicyclo[3.3.3]undecane ( 1 ), is described. Stannane 1 was prepared by the disproportionation of N(CH 2 CH 2 CH 2 SnBu 3 ) 3 and SnCl 4 at 70–100°C. This reaction requires the addition of water or an alcohol to proceed efficiently. Under typical conditions, 1 was isolated in 50–55% yield after a simple acid/base extraction sequence.

[formula: see text] A short synthesis of carbapenem 1 is described. They key step involves the cross-coupling of an enol triflate with an amino-substituted sp3 carbon. This cross-couping, which allows the introduction of the complete side chain in one step, utilizes a stannatrane as the heteroalkyl transfer reagent.

A simple and scalable procedure for the preparation of chiral ligands 1and 2from trans-1,2-diaminocyclohexane and 2-picolinic acid is described.

The synthesis and antibacterial activity of several 7 beta-[1-(2-aminothiazol-4-yl)-1-cyclopropanecarboxyamido]cep hem derivatives (1) are described. The structure-activity relationships of 1 are also presented.

Two new 3-cyano-3-cephem derivatives, potassium 3-cyano-3-cephem-4-carboxylate (2) and potassium 7α-phenylacetamido-3-cyano-3-cephem-4-carboxylate (3), were prepared from 7β-aminocephalosporanic acid. Compounds 2 and 3 showed only weak β-lactamase inhibitory activity in contrast to sodium 7α-[(1R)-1-hydroxyethyl]-3-cyano-3-cephem-4-carboxylate (1), indicating the important role of the 7α-(1-hydroxyethyl) substituent for β-lactamase inhibitory activity.

The main focus of this report was to investigate the relationship between β-lactamase inhibitory activity and oxidative state at the 1 position of 7α-hydroxyethyl cephem derivatives

A key intermediate for 2-(functionalized-methyl)-1-beta-methylcarbapenems, 3-[(1R)-1-t-butyldimethylsilyloxyethyl]-4-[(2R)- 4-halo-3-oxo-2-butyl]azetidinone, was prepared efficiently from a commercially available carboxylic acid in 3 steps.

Intramolecular reductive amination is utilized as a key 8-membered ring-forming cyclization reaction to construct the novel bicyclic hydroxylamine hemi-ketal ring system of FR900482.

A series of 7 alpha-hydroxyethyl-1-oxacephems (1) was synthesized. The main focus of this study was to investigate biological activity relationships between 1-oxacephems (1) and the corresponding cephems (2). Replacement of the sulfur atom of 2 by the oxygen atom caused an enhancement of antibacterial activity, although the antibacterial activity of 1 was not high enough. Additionally 1 showed beta-lactamase inhibitory activity, especially against cephalosporinase. However, the potency was lower than that of 2.

Swainsonine, a potential immunoregulator, was synthesized from D-mannose via an intermediate, methyl 4,8-imino-2,3-O-isopropylidene-4,6,7,8-tetradeoxy-α-D-manno-octopyranoside.

3,7-Dihydroxy- and 3-substituted 7-hydroxypyrazolo[4,3-d]pyrimidines were synthesized from diethyl oxaloacetate and ethyl acylpyruvates via ethyl 4-amino-5-oxo-2-pyrazoline-3-carboxylate hydrochloride and ethyl 5-substituted 4-amino-3-pyrazolecarboxylates, respectively.

The novel, semisynthetic pseudodisaccharide antibiotic, 3-O-demethylsporaricin A, was synthesized via 3-O-demethylsporaricin B obtained by glycosidation of its aminocyclitol part. The aminocyclitol part was synthesized as D,L-form from D,L-(1,2,3/4,5,6)-1,4-bis(benzyloxy-carbonylamino)-5,6-O-isopropyl idene-2,3,5,6-cyclohexanetetraol via three key steps, namely, deoxygenation, inversion of a hydroxyl group, and N-methylation. The physical and biological properties of synthetic 3-O-demethylsporaricin A and an authentic sample derived from sporaricin B were identical.

Two stereoisomers of swainsonine, (1S,2S,8S,8aR)-1,2,8-trihydroxyoctahydroindolizine and the corresponding (1S,2R,8S,8aR) derivative, were synthesized from D-glucose via one step cyclization to the 5-oxo-1,2,8-trihydroxyoctahydroindolizine derivative.

Synthese du (1,2,4/5,6)-tri-O-acetyl-1,4,6 bis-benzyloxycarbonylamino-2,5 N-methyl-5 cyclohexanetriol-1,4,6 a partir de (1,2,3/4,5,6)-bis-benzyloxycarbonylamino-1,4 O-isopropylidene-2,3 cyclohexanetetraol-2,3,5,6

Various 5-trimethylsiloxyoxazoles were synthesized by the silylation of 2-oxazolin-5-ones using chlorotrimethylsilane and triethylamine in high yields. Diels–Alder reaction of the siloxyoxazoles with N-phenylmaleinimide or dimethyl maleate afforded the corresponding substituted pyridines in high yields. This method was applied to the synthesis of Vitamin B6 derivatives starting from N-formylalanine.

Various silyl enol ethers gave the corresponding mono benzyl products in moderate to good yields by the reaction with benzyl bromide in the presence of silver perchlorate in dichloromethane at −78–...

Swainsonine, a potential immunoregulator, was synthesized from D-mannose via an intermediate, methyl 4,8-imino-2,3-O-isopropylidene-4,6,7,8-tetradeoxy-α-D-manno-octopyranoside.

Various 5-trimethylsiloxyoxazoles were synthesized by the silylation of 2-oxazolin-5-ones using chlorotrimethylsilane and triethylamine in high yields. Diels–Alder reaction of the siloxyoxazoles with N-phenylmaleinimide or dimethyl maleate afforded the corresponding substituted pyridines in high yields. This method was applied to the synthesis of Vitamin B6 derivatives starting from N-formylalanine.

3,7-Dihydroxy- and 3-substituted 7-hydroxypyrazolo[4,3-d]pyrimidines were synthesized from diethyl oxaloacetate and ethyl acylpyruvates via ethyl 4-amino-5-oxo-2-pyrazoline-3-carboxylate hydrochloride and ethyl 5-substituted 4-amino-3-pyrazolecarboxylates, respectively.

Two stereoisomers of swainsonine, (1S,2S,8S,8aR)-1,2,8-trihydroxyoctahydroindolizine and the corresponding (1S,2R,8S,8aR) derivative, were synthesized from D-glucose via one step cyclization to the 5-oxo-1,2,8-trihydroxyoctahydroindolizine derivative.

The synthesis and antiviral activity of various aminoglycoside derivatives having a palmitoyl group are described. All of these aminoglycoside derivatives exhibited almost the same excellent antiviral activity against herpes simplex virus type I and influenza virus.

The synthesis and antiviral activity of 1-N-palmitoyl- or 1-N-(3-hydroxytetradecanoyl)-kanamycin A derivatives (7, 8) having various type of acyl substituents at the N-3" position were investigated. The structure-activity relationships between the antiviral activity and the substituent at the N-3" position is described. In this series, 3"-N-acetyl-1-N-palmitoylkanamycin A (7c) showed the excellent antiviral activity against HSV-I and influenza virus. Further, we examined the synthesis and the antiviral activity of 3"-N-glycylkanamycin A derivatives (9) having a higher-acyl group at the N-1 position. The 3"-N-glycyl-1-N-pentadecanoylkanamycin A (9a) also exhibited excellent antiviral activity.

The synthesis and antiviral activity of 3''-N-trifluoroacetylkanamycin A derivatives (6) having higher acyl group at the N-1 position are described. On the basis of the structure-activity relationships between antiviral activity and alkyl chain length in an acyl group at the N-1 position, analogs (6f approximately I) having higher alkylcarbonyl group exhibited antiviral activity against not only HSV-I but also influenza virus. Analogs (6q approximately v) having higher alkyloxycarbonyl group showed antiviral activity against HSV-I. In addition, kanamycin A derivatives (6n, o, y, z) possessing higher alkylcarbonyl group with a functional group, higher alkylaminocarbonyl group, and higher alkylthiocarbonyl group had antiviral activity against HSV-I. The analog (6h) showed a broad antiviral spectrum against both DNA (HSV-I, HSV-II, VZV) and RNA (influenza) viruses.

Various silyl enol ethers gave the corresponding mono benzyl products in moderate to good yields by the reaction with benzyl bromide in the presence of silver perchlorate in dichloromethane at −78–...