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A practical route for the synthesis of both enantiomers of a functionalized bicyclo[3.2.1]octenone, which is potentially useful as a versatile chiral building block, has been developed from 1,4-cyclohexanedione monoethylene acetal by employing proline-catalyzed diastereoselective intramolecular aldolization and lipase-mediated kinetic resolution as the key steps. The synthetic utility of the bicyclo[3.2.1]octenone has been demonstrated by the conversion into a chiral bicyclo[5.3.0]decane, which should serve as the key intermediate for the synthesis of the pseudoguaianolide class of antitumor sesquiterpenes.

A facile enantio- and diastereocontrolled construction of 18-keto-pseudoyohimbane from a bicyclo[3.2.1]octane chiral building block has been developed employing a tandem retro-aldol and Pictet–Spengler sequence. The epimerization of the resulting pseudoyohimbane into the corresponding yohimbane derivative has also been achieved.

The ring-contraction of the enedione epoxide obtained from the adduct of benzoquinone and cyclopentadiene is mainly affected by the amount of base used. Excellent yields (>80%) of the ring-contracted product were consistently obtained when the epoxide was treated with a 0.5 equiv. of ethanolic sodium hydroxide in ethanol. The versatility of the chiral building block accessible from the ring-contracted product has also been demonstrated by an alternative diastereocontrolled synthesis of (+)-tanikolide, a toxic and antifungal marine natural product isolated from Lyngbya majuscula.

Lithium triethylborohydride has been found to be a superior and selective reagent for the removal of tertiary N-acyl protecting groups. The reagent selectively removes tertiary amide acyl functionality without affecting secondary amide functionality even when they are present in the same molecule. Some tertiary carbamates may be also removed under the same conditions.

Efficient methodology for the preparation of the artificial levoglucosenone-type chiral building blocks having a bicyclo [3. 2. 1] octane framework has been developed along with two new routes to both enantiomers of levoglucosenone. Because of their inherent stereochemical and chemical nature with a sterically biased structure containing an enone, a masked formyl and a 1, 2-glycol, and a hydroxymethyl functionalities, these chiral building blocks allow the diastereo- and enantio-controlled construction of a wide variety of natural products.

An enantio- and diastereoselective synthesis of the methyl ester of 3,5-trans-(3R,5R)-carbapenam-3-carboxylic acid from 3-hydroxypyridine via (2R,5S)-trans-5-acetoxy-2-allylpiperidine has been achieved by employing the piperidine–pyrrolidine ring-contraction reaction as the key step. The synthesis indicates that the configuration of the naturally occurring 3,5-trans-carbapenam-3-carboxylic acid is not the revised (3S,5S), but rather the originally assigned (3R,5R) configuration.

An enantioselective route to the key intermediate leading to (+)-vernolepin, an antitumor sesquiterpene, isolated from Vernonia hymenolepis, has been developed starting from the chiral building block having a bicyclo[3.2.1]octane framework accessible by either enzymatic or catalytic kinetic resolution.

A new route to the aldopentoses, ribose and lyxose, and the aldohexoses, talose and gulose, has been developed using chiral building blocks containing a bicyclo[3.2.1]octane framework by employing a photochemical decarbonylation reaction as the key step.

The intramolecular ene reaction of the 1,6-diene on a bicyclo[3.2.1]octane framework proceeds in a highly diastereoselective manner to form a trisubstituted pyrrolidine on the pyran ring in excellent yield. Its stereochemistry has been determined unambiguously by converting it into the known compound serving as a key intermediate of (−)-kainic acid.

A synthesis of both enantiomers of levoglucosenone from acrolein dimer has been developed by employing lipase-mediated kinetic hydrolysis. Thus, acrolein dimer is transformed into racemic dihydrolevoglucosenone by sequential hydride reduction, oxidative acetalization, and Swern oxidation. Employing Saegusa-Larock conditions, dihydrolevoglucosenone is transformed into racemic levoglucosenone. The lipase-mediated resolution was best carried out under hydrolysis conditions with the endo-acetate generated from racemic levoglucosenone to give rise to highly enantioenriched (+)-alcohol and enantiopure (−)-acetate serving as the precursors of enantiopure levoglucosenone having the corresponding chirality.

A potential stereocontrolled route to acromelic acids, neuroexitatory amino acids isolated from the mushroom Clitocybe acromelalga , has been developed by employing either concurrent Chugaev-ene reaction or retro-Diels–Alder-ene reaction and regioselective pyridinecarboxylate formation reaction as the key steps.

A procedure for regio- and diastereocontrolled annulation of a 3-methylcyclopentenone moiety on a cyclopentenol double bond has been developed by employing the Pauson–Khand reaction in the presence of a promoter having reductive potential. During the examination, a novel substrate specific 3-hydroxycyclopentanone formation reaction was also discovered.

Starting from enantiopure 4-cumyloxy-2-cyclopenten-1-one, a route to 5- and 6-substituted hyropyran-2-ones has been developed. The method has achieved the synthesis of 4,5- cis - and 4,5- trans -5-ethyl-4-hydroxytetrahydropyran-2-ones assigned to marine natural products simplactones A and B to disprove the former and revise the latter of the proposed structures.

A new diastereocontrolled route to three alkaloids having a quaternary benzylic stereogenic center, (−)-physostigmine, (−)-physovenine, and (−)-aphanorphine, has been developed using enantiopure 7,7-dimethyl-6,8-dioxabicyclo[3.3.0]oct-3-en-2-one as a synthetic equivalent of chiral cyclopentadienone.

[reaction: see text] Diastereoselective synthesis of racemic 3,4-dimethoxy-7-morphinanone from racemic 2-(2,3-dimethoxyphenyl)cyclohexen-1-ol has been achieved. The relative structure has been determined by transformation of the product into the known 3, 4-dimethoxy-6-morphinanone. Resolution of the starting cyclohexenol has also been accomplished for use in a future enantiocontrolled synthesis of morphine.

An insect aggregate pheromone (+)-frontalin and a marine antibiotic (−)-malyngolide, both bearing a quaternary stereogenic center in their molecules, have been synthesized in diastereocontrolled manner by employing a catalytic asymmetric hydrogen transfer reaction as the key step. An inversion protocol allowing enantioconvergent use of the other enantiomeric resolved product has also been devised.

A new synthesis of the C 28 –C 34 segment of FK-506 has been developed using a chiral building block having a 6,8-dioxabicyclo[3.2.1]octane framework by employing a ring-closing metathesis reaction as the key step.

An efficient enantiodivergent route to α-cuparenone, a sesquiterpene isolated in both enantiomeric forms, has been developed utilizing a chiral cyclopentanoid starting material having a latent meso structure.

The patient was 59-year-old man. He had a selective proximal vagotomy with pylorectomy and a reconstruction of gastrojejunostomy for duodenal ulcer 22 years ago. Nov. 1998 he visited our clinic because of epigastric pain and received gastric fiberscopy to be diagnosed as the gastric cancer that was located just oral to the anastomosis site of the stomach and the jejunum. Gastrectomy was performed safely. Gastric cancer following vagotomy is a rare entity and there have been only 22 cases in the Japanese literature. In our institution, vagotomy has been performed in a series of 395 patients from 1972 to 1999, and this patient was the third case that experienced gastric cancer after vagotomy. We present this third case with a review of the literature in terms of the correlation between vagotomy and development of gastric cancer.

Racemic endo-4-acetoxybicyclo[3.2.1]oct-2-ene furnishes enantiopure (+)-bicyclo[3.2.1]oct-3-en-2-one and its dihydro derivative leaving enantiopure (+)-endo-4-acetoxybicyclo[3.2.1]oct-2-ene in a phosphate buffer solution in the presence of a lipase (Candida antarctica) and palladium(II) chloride. Utilizing the products, a diastereocontrolled route to some cyclopentanoid monoterpenes has been established.

A chiral tricyclic diol, serving as a synthetic equivalent of chiral methyl 2,5-dihydroxycyclohexane-1,4-dienecarboxylate, has been prepared in both enantiomeric forms by employing a lipase-mediated kinetic resolution in vinyl acetate.

A RuII-chiral amine complex has accomplished oxidative resolution of the 2-cyclopentene-1-ols having a bicyclo[2.2.1]heptene background to afford the cyclopentenones and the cyclopentenols both in good to excellent optical and chemical yields by an asymmetric hydrogen transfer reaction. The hydrogen transfer occurred selectively at the allylic methine hydrogen even though allylic methylene hydrogens are present at the same relative position.

A new lipase-mediated methodology has been devised for the preparation of single enantiomeric trans -epoxides from unsymmetrical cis -olefin precursors via enantiomeric convergence of racemic intermediates.

(+)-Juvabione and (+)-epijuvabione, natural sesquiterpenes exhibiting insect juvenile hormone activity, have been synthesized from (±)-norcamphor via the both enantiomeric intermediates having bicyclo[3.2.1]octane framework by employing a lipase-mediated kinetic ester-hydrolysis reaction and cyclopropane ring-expansion reaction as the key steps.

Efficient methodology for the preparation of two enantiopure cyclohexanoids having a bicyclo [2.2. 1] octene background has been established starting from the same meso ene-1, 4-diol by employing enzymatic and catalytic asymmetric desymmetrization procedures. On the basis of their inherent convex-face selectivity and thermal fragility, we utilize these chiral tricycles as synthetic equivalents of chiral p-benzoquinone and its hydro derivatives whose potential uses have been demonstrated by diastereo- and enantio-controlled synthesis of a wide variety of biologically active natural products.

Three procedures for the transformation of achiral 1-(3,4-dimethoxyphenyl)-cyclohexene into enantiomerically pure 2-(3,4-dimethoxyphenyl)cyclohex-2-en-1-ol have been established at first. Utilizing the (−)-cyclohexenol thus obtained, the four titled Sceletium alkaloids have been synthesized in the natural enantiomeric forms.

Racemic 3-hydroxy-2-hydroxymethyl- endo -tricyclo[5.2.1.0 2,6 ]-dec-4,8-diene serving as a synthetic equivalent of 2-hydroxymethylcyclopentadien-5-ol has been resolved by employing lipase-mediated kinetic transesterification with vinyl acetate in an organic solvent.

Determination of fourteen alkaloids, toxic Aconitum alkaloids, aconitine, mesaconitine, jesaconitine, hypaconitine and deoxyaconitine, and their hydrolysis products, benzoylaconines and aconines, have been established using capillary liquid chromatography (LC) fast atom bombardment mass spectrometry (FAB-MS) with a frit interface. Protonated molecular ions were observed as base peaks in the FAB-MS for these fourteen alkaloids. All the alkaloids were simultaneously quantified with linear gradient LC elution by solvent mixture of acetonitrile and 0.3% trifluoroacetic acid using selected ion monitoring of the protonated molecular ions. The calibration curves of these alkaloids were linear in injection amounts ranging from 5 to 500 pg, and their detection limits were 1 pg per injection (S/N=3). Solid-phase extraction using Sep-Pak Plus PS-1 was also investigated to clean-up and concentrate alkaloids in blood and urine samples, and showed satisfactory recoveries. This capillary LC-frit-FAB-MS method enables determination of low levels of Aconitum alkaloids in blood and urine samples, coupled with solid-phase extraction.

A general procedure for a chemoselective removal of the allyl (2-propenyl) functionality on basic, neutral and acidic nitrogens by diisobutylaluminum hydride or trimethylaluminum in the presence of a catalytic amount of (dppp)NiCl2 has been developed.

An enantiocontrolled route to the 19-oxygenated pentacyclic Strychnos alkaloids has been demonstrated by the stereoselective synthesis of (−)-19( S )-acetoxy- N 1 -acetyl-20-epitubifolidine

A new enantiocontrolled synthesis of (−)- exo -isobrevicomin, isolated from male mountain pine beetles, Dendroctonus ponderosae , has been established starting from 5-ethyl-2-furfural by employing AD-mix-induced asymmetric induction and oxidative furan ring-expansion reaction as the key steps.

A tricyclic meso 1,2-enediol bis(trimethylsilyl) ether having an endo-tricyclo[4.2.1.02,5]nonene framework has been asymmetrically desymmetrized by protonation with a complex generated from (S)-BINOL monoisopropyl ether (BINOL-Pri) and tin tetrachloride to give the optically enriched acyloin in 90% ee. The chiral acyloin thus obtained has been transformed into two versatile chiral building blocks, (−)-ketodicyclopentadiene and (−)-ketotricyclononene, in optically pure forms via a sequence involving concurrent enzymatic acetylation and optical purification. © 1997 Elsevier Science Ltd.

An expedient route to a series of monoalkyl ethers of optically active bi-β-naphthol has been established by use of the Mitsunobu reaction.

A meso -1,4-enediol bis -silyl ether 2 having bicyclo[2.2.1]heptene background has been transformed diastereo- and enantioselectively into (−)-malyngolide 1 , an antibiotic isolated from the blue-green marine algae, Lyngbya majuscula , via Rh(I)-( R )BINAP-catalyzed asymmetrization and diastereoselective modification of the optically active product thus obtained.

Kinetic resolution of tricyclic acyloins, endo -3-hydroxytricyclo[4.2.1.0 2,5 ]non-7-en-4-one and endo -3-hydroxytricyclo[4.2.2.0 2,5 ]dec-7-en-4-one, and their acetates has been examined using a lipase. It has been found that a facile and stereoselective kinetic resolution occurs both in organic solvent and an aqueous solution in enantiocomplementary ways to afford both enantiomers of the acyloins and their acetates in enantiomerically pure forms. Enantiomerization of (+)-acyloins leading to (−)-acyloin acetates has also been achieved by the same lipase in an organic solvent by addition of a catalytic amount of triethylamine.

The absolute configuration of (+)-sporochnol A, the fish deterrent from the Caribbean marine alga Sporochnus bolleanus, has been established as S based on the stereocontrolled synthesis of its (R)-(−)-enantiomer from (S)-epichlorohydrin.

A new stereocontrolled route to (−)-kainic acid, the representative of the kainoid amino acids and exhibiting insecticidal, anthelmintic and neuroexcitatory properties, has been devised in an enantioconvergent way using either (+)- or (−)-ketodicyclopentadiene as the starting material by employing a concurrent retro-Diels-Alder reaction and intramolecular ene reaction as the key step.

The katsuki-Sharpless asymmetric epoxidation reaction of meso syn-2,3-bis-endo- and exo-allyl alcohols on a bicyclo[2.2.1]heptane framework took place regio- and stereo-selectively in a unilateral way to give the corresponding mono-epoxidation products as the major product.

(+)-Estrone has been synthesized in an enantioconvergent manner from racemic 4- tert -butoxy-2-cyclopentenone via contrasteric Diels-Alder reaction and lipase-mediated kinetic transesterification as the key steps.