Determination of the absolute configuration of the male aggregation pheromone, 2-methyl-6-(4′-methylenebicyclo[3.1.0]hexyl)hept-2-en-1-ol, of the stink bug Erysarcoris lewisi (Distant) as 2Z,6R,1′S,5′S by its synthesis

Lipase-catalyzed asymmetric acetylation of a mixture of (6R,1′S,4′S,5′R)- and (6R,1′R,4′R,5′S)-7′-norsesquisabinen-4′-ol (3) afforded a separable mixture of the recovered former and the acetate of the latter. The recovered alcohol was oxidized to (6R,1′S,5′R)-sesquisabina ketone (2), whose absolute configuration could be assigned by its CD comparison with (1R,5S)-sabina ketone (4). Conversion of (6R,1′S,5′R)-sesquisabina ketone (2) to the bioactive pheromone revealed the stereostructure of the male aggregation pheromone of the stink bug Erysarcoris lewisi (Distant) to be (2Z,6R,1′S,5′S)-2-methyl-6-(4′-methylenebicyclo[3.1.0]hexyl)hept-2-en-1-ol (sesquisabinen-1-ol, 1).     

Studies on the Michael addition of naphthoquinones to sugar nitro olefins: first synthesis of polyhydroxylated hexahydro-11H-benzo[a]carbazole-5,6-diones and hexahydro-11bH-benzo[b]carbazole-6,11-diones

A strategy for the synthesis of the novel (6bR,7R,8S,9S,10S,10aR)-8-(benzyloxy)-7,9,10-trihydroxy-6b,7,8,9,10,10a-hexahydro-11H-benzo[a]carbazole-5,6-dione is reported. The key steps were the Michael addition of 2-hydroxy-1,4-naphthoquinone to 1-nitrocyclohexene or 3-O-benzyl-5,6-dideoxy-1,2-O-isopropylidene-6-nitro-α-d-xylo-hex-5-enefuranose and the diastereoselective intramolecular Henry reaction of 3-O-benzyl-5,6-dideoxy-5-C-(3′-hydroxy-1′,4′-naphthoquinon-2′-yl)-1,2-O-isopropylidene-6-nitro-α-d-glucofuranose to give the key (1S,2S,3S,4R,5R,6R)-3-(benzyloxy)-1,2,4-trihydroxy-5-(3′-hydroxy-1′,4′-naphthoquinon-2′-yl)-6-nitrocyclohexane. When 2-hydroxy-1,4-naphthoquinone was replaced by (1,4-dimethoxynaphthalen-2-yl)lithium, the novel (1R,2S,3S,4R,4aS,11bS)-2-(benzyloxy)-1,3,4-trihydroxy-1,2,3,4,4a,5-hexahydro-11bH-benzo[b]carbazole-6,11-dione was obtained.     

Synthesis of (−)-(1′S,4aS,8aR)- and (+)-(1′S,4aR,8aS)-4a-ethyl-1-(1′-phenylethyl)-octahydroquinolin-7-ones

A synthesis of the enamine (−)-(1′S)-5-ethyl-1-(1′-phenylethyl)-1,2,3,4-tetrahydropyridine 4 and its application in a synthesis of (−)-(1′S,4aS,8aR)- and (+)-(1′S,4aR,8aS)-4a-ethyl-1-(1′-phenylethyl)-octahydroquinolin-7-ones 5 and 6 is described. In addition, an X-ray study of 6 is reported. Finally, the preparation of (+)-(4aS,8aR)-4a-ethyl-octahydroquinolin-7-one 7 is described.     

Synthesis and odor of optically active trans-2,2,6-trimethylcyclohexyl methyl ketones and their related compounds

The synthesis characterized by cationic olefin cyclizations accomplished using ketone enol esters and odor of novel (1R,6S)- and (1S,6R)-2,2,6-trimethylcyclohexyl methyl ketones (5) are described. The stereoselective syntheses of (E)-(1R,6S)- and (E)-(1S,6R)-1-(2,2,6-trimethylcyclohexyl)-2-buten-1-one (6) and (1R,6S)-ethyl 2,2,6-trimethylcyclohexylcarboxylate (7), useful raw materials for flavor and fragrance, starting from the (1R,6S)- and (1S,6R)-5 are also described.     

Total synthesis of (4R,5S,6E,14S)- and (4R,5S,6E,14R)-cystothiazoles F

Total synthesis of (4R,5S,6E,14S)- and (4R,5S,6E,14R)-cystothiazoles F 3 was achieved from the chiral bithiazole-type primary alcohols [(S)- and (R)-4-ethoxycarbonyl-2′-(1-hydroxymethylethyl)-2,4′-bithiazoles 8], which were obtained based on the enzymatic resolution of racemic alcohol 8 and its acetate 9. From a direct comparison by means of chiral HPLC between natural cystothiazole F 3 and synthetic compounds [(4R,5S,6E,14S)- and (4R,5S,6E,14R)-cystothiazoles 3], natural cystothiazole F 3 was found to be a 33:67 diastereomeric mixture [(4R,5S,6E,14S)-3:(4R,5S,6E,14R)-3 = 33:67].     

Stereoselective synthesis of 3,4,5,6-tetrahydroxycyclohexyl β-amino acid derivatives

Stereoselective syntheses of racemic (1S,2R,3R,4R,5S,6R)- and (1S,2R,3R,4S,5S,6R)-3,4,5,6-tetrahydroxy derivatives of 2-aminocyclohexanecarboxylic acid have been achieved by a stereospecific Diels-Alder reaction between furan and maleic anhydride, a Curtius rearrangement and hydroxylation reactions.     

Synthesis of (+)-1,3,5,7 -tetrakis[2-(1S,3S,5R,6S,8R,10R)-D3-trishomocubanylbuta-1,3-diynyl]adamantane : The first optically active organic molecule with t symmetry and of known absolute configuration

(-)-(1S,3S,5R,6S,8R,10R)-Trishomocubanethanoic acid (5) of known absolute configuration and absolute rotation was converted into (+)-(1S,3S,5S,6S,8R,10R)-2-bromoethynyl-D₃-trishomocubane (27) of C₃ symmetry. 1,3,5,7-Tetraethynyladamantane (22), with Td symmetry, was prepared from 1,3,5,7-tetrakis(hydroxymethyl)adamantane(13). Coupling of the C₃-component 27 with the Td component 22 was successfully accomplished by Chodkiewicz and Cadiot's procedure providing (+)-1,3,5,7-tetrakis[2-(1S,3S,5R,6S,8R,10R)-D₃-trishomocubanylbuta-1,3-diynyl]adamantane(4) whose highest attainable static and time-averaged dynamic symmetry are T and (C₃)⁴ XXX T,respectively.     

A novel and versatile method for the enantioselective syntheses of tropane alkaloids

A full account of the novel and flexible approach to hydroxylated 8-azabicyclo[3,2,1]octan-3-ones and 9-azabicyclo[3,3,1]nonan-3-ones is presented.Using keto-lactams as the starting materials,this two-step method consists of silyl enol ether formation with TBDMSOTf,lactam activation with Tf2O/DTBMP,and halide-promoted cyclization.Radical dechlorination of the resulting 1-halotropan-3-ones led to the corresponding hydroxylated tropan-3-ones,which can be hydrogenated to yield3,6-dihydroxytropanes.Starting from optically active keto-lactams,the method has been applied to the enantioselective syntheses of(+)-(1S,3S,5R,6S)-pervilleine C(6),(+)-(1S,3R,5S,6R)-valeroidine(3),(+)-(1S,3S,5R,6S)-dibenzoyloxytropane(8),and(+)-(1S,3S,5R,6S)-merredissine(9).     

Total synthesis of natural (+)-hyacinthacine A6 and non-natural (+)-7a-epi-hyacinthacine A1 and (+)-5,7a-diepi-hyacinthacine A6

Naturally occurring (1S,2R,3R,5R,7aR)-1,2-dihydroxy-3-hydroxymethyl-5-methylpyrrolizidine [(+)-hyacinthacine A₆, 2] together with unnatural (1S,2R,3R,7aS)-1,2-dihydroxy-3-hydroxymethylpyrrolizidine [(+)-7a-epi-hyacinthacine A₁, 3] and (1S,2R,3R,5S,7aS)-1,2-dihydroxy-3-hydroxymethyl-5-methylpyrrolizidine [(+)-5,7a-diepi-hyacinthacine A₆, 4] have been synthesized from a DALDP derivative [5, (2R,3S,4R,5R)-3,4-dibenzyloxy-2′-O-tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine], as the homochiral starting material. The synthetic process employed took advantages of Wittig methodology followed by internal lactamization, in the case of (+)-7a-epi-hyacinthacine A₁ (3), and reductive amination for (+)-hyacinthacine A₆ (2) and (+)-5,7a-diepi-hyacinthacine A₆ (4).     

Synthesis of both the enantiomers of endo-brevicomin,the aggregation pheromone of Dryocoetes autographus

(1R,5S,7S)-(+)-endo-Brevicomin (7-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]octane) and its (1S,5R),7(R)-(?)-isomer were synthesised employing the Sharpless asymmetric epoxidation as the key-step.     

Stereocontrolled transformation of nitrohexofuranoses into cyclopentylamines via 2-oxabicyclo[2.2.1]heptanes. Part 6: synthesis and incorporation into peptides of the first reported 2,3-dihydroxycyclopentanecarboxylic acid

Herein we report the intramolecular alkylation of nitronates of methyl-5-O-benzyl-3,6-deoxy-6-nitro-β-d-glucofuranoside and methyl-5-O-benzyl-3,6-deoxy-6-nitro-α-d-glucofuranoside into the corresponding 2-oxabicyclo[2.2.1]heptane derivatives. Similarly, methyl-3-O-benzyl-5-deoxy-5-nitromethyl-β-d-xylofuranoside and methyl-3-O-benzyl-5-deoxy-5-nitromethyl-α-d-xylofuranoside were cyclized to (1R,3R,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane and (1R,3S,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane, respectively. These 2-oxabicyclo[2.2.1]heptane derivatives were eventually transformed into enantiopure methyl (1S,2S,3R,4S,5R)-2-amino-2,3-dihydroxycyclopentanecarboxylate and this novel β-amino acid was incorporated into peptides.     

Stereoselective synthesis of 3-deoxy-piperidine iminosugars from l-lysine

A new method using electrochemical oxidation and/or OsO₄ oxidation has been used for the stereoselective synthesis of 2,3,6-trihydroxylated (5S)-piperidine derivatives. The electrochemical method was successively used for the conversion of N-protected piperidines to N-protected 1-methoxypiperidines and for the conversion of 2,3-didehydro-1-methoxypiperidine derivatives to 2,3-trans-1,2,3-triacetoxypiperidine derivatives. These triacetates were easily transformed into (2S,3S)-6-triacetoxy-(5S)-methylpiperidine and (2R,3R)-6-triacetoxy-(5S)-methylpiperidine. In addition, the 2,3-cis-dihydroxylation of 2,3-didehydro-1-methoxypiperidine derivatives with OsO₄ afforded (2R,3S)-6-triacetoxy-(5S)-methylpiperidine and (2S,3R)-6-triacetoxy-(5S)-methylpiperidine.     

Two diasteoisomers of 5-hydroxy-6-methylpipecolic acid from seeds of Fagus silvatica L.

Two diastereoisomers of 5-hydroxy-6-methylpipecolic acid have been isolated from beechnuts. The configurations of the two amino acids have been assigned as (2S, 5S, 6S) (1) and (2S, 5R, 6S) (2). The determination of structure and configuration for the two new amino acids is mainly based on spectroscopic and rotatory evidence. The ¹³C-NMR and ¹H-NMR spectra of the three ionic forms of the two amino acids and of S-pipecolic acid and (2S, 5R)-5-hydroxypipecolic acid and the CD-curves of the cations and amfoions of 1, 2, and (2S, 5R)-5-hydroxypipecolic acid have been recorded.     

Synthesis of the ABC-ring models of goniodomin A: preference for the unnatural configuration at C11 of the BC-ring in a non-macrocyclic model system

To confirm the natural relative stereochemistry of the ABC-ring of goniodomin A (1), the corresponding three stereoisomeric compounds, (2R,5S,6S,7S,9S,11R,15S)-, (2R,5S,6S,7R,9R,11S,15R)-, and (2R,5S,6S,7R,9R,11R,15S)-isomers (2, 3, and 5, respectively), were stereoselectively synthesized using a Nozaki-Hiyama-Kishi reaction as a key step. It was also found that a (2R,5S,6S,7R,9R,11S,15S)-isomer (4), corresponding to the absolute configuration of 1 recently proposed by Sasaki, was not detected during the formation of 5 from a common ketodiol substrate under acid-catalyzed spiroacetalization conditions. This would be attributable to the absence of a macrocyclic framework.     

Absolute configuration of gomadalactones A, B and C, the components of the contact sex pheromone of Anoplophora malasiaca

Absolute configuration of gomadalactones A (1), B (2) and C (3), the pheromone components of the white-spotted longicorn beetle (Anoplophora malasiaca) was assigned as (1S,4R,5S)-1, (1R,4R,5R)-2 and (1S,4R,5S,8S)-3 by comparing their published CD spectra with those of (1R,5R)-(+)-4,4,8-trimethyl-3-oxabicyclo[3.3.0]oct-7-ene-2,6-dione (4) and (1S,5R,8S)-(+)-4,4,8-trimethyl-3-oxabicyclo[3.3.0]octane-2,6-dione (5) prepared from (R)-(−)-carvone (6).     

An approach to an asymmetric synthesis of stemofoline

A stereoselective Mannich reaction between an (S)-tert-butylsulfinimine and methyl (S)-4-benzyloxy-3-methylbutanoate followed by treatment with acid and N-protection was used to prepare methyl (2R,3S)-2-[(S)-2-benzyloxy-1-methylethyl]-3-tert-butoxycarbonylamino-6-methylenedecanoate. This was taken through to methyl (4R,5S)-4-[(S)-2-benzyloxy-1-methylethyl]-5-tert-butoxycarbonylamino-3,8-dioxododecanoate which on treatment with trifluoroacetic acid cyclised stereoselectively to give (1R,2S,4R,5S)-4-[(S)-2-benzyloxy-1-methylethyl]-1-butyl-2-methoxycarbonyl-8-tert-butoxycarbonyl-3-oxo-8-azabicyclo[3.2.1]octane, a potential precursor of stemofoline. Reduction and N-deprotection of this ketone gave (1R,2S,3R,4R,5S)-4-[(S)-2-benzyloxy-1-methylethyl]-1-butyl-2-methoxycarbonyl-8-azabicyclo[3.2.1]octan-3-ol the structure of which was confirmed by X-ray diffraction.     

Biotransformation of (−)-α-Bisabolol by Absidia coerulea

(−)-α-Bisabolol, a bioactive monocyclic sesquiterpene alcohol, has been used in pharmaceutical and cosmetic products with anti-inflammatory, antibacterial and skin-caring properties. However, the poor water solubility of (−)-α-bisabolol limits its pharmaceutical applications. It has been recognized that microbial transformation is a very useful approach to generate more polar metabolites. Fifteen microorganisms were screened for their ability to metabolize (−)-α-bisabolol in order to obtain its more polar derivatives, and the filamentous fungus Absidia coerulea was selected for scale-up fermentation. Seven new and four known metabolites were obtained from biotransformation of (−)-α-bisabolol (1), and all the metabolites exhibited higher aqueous solubility than that of the parent compound 1. The structures of newly formed metabolites were established as (1R,5R,7S)- and (1R,5S,7S)-5-hydroxy-α-bisabolol (2 and 3), (1R,5R,7S,10S)-5-hydroxybisabolol oxide B (4), (1R,7S,10S)-1-hydroxybisabolol oxide B (5), 12-hydroxy-α-bisabolol (7), (1S,3R,4S,7S)- and (1S,3S,4S,7S)-3,4-dihydroxy-α-bisabolol (8 and 10) on the basis of spectroscopic analyses. These compounds could also be used as reference standards for the detection and identification of the metabolic products of 1 in the mammalian system.     

A novel chemo-multienzymatic synthesis of bioactive cyclophellitol and epi-cyclophellitol in both enantiopure forms

A new route to synthesize cyclophellitol and epi-cyclophellitol from racemic starting materials in enantiopure forms has been developed. The synthesis involves a multi-enzymatic biotransformation pathway of the novel cyano-cyclitol (1R,4S,5R,6R)/(1S,4R,5S,6S)-4,5,6-trihydroxycyclohex-2-enecarbonitrile by a cooperative use of lipase, nitrile hydratase, and amidase.     

Stereoselective carbon–carbon bond forming reactions of chiral cyclopent-2-enone and cyclopentene-1-methanol,both spiro-connecting a 1,2:5,6-di-O-isopropylidene-α-d-glucofuranosyl ring

The conjugate additions of a variety of organocopper reagents or dimethyl malonate anion to a spirocyclic cyclopent-2-enone connecting a 1,2:5,6-di-O-isopropylidene-α-d-glucofuranosyl ring as a constituent of the spiro structure, namely (1S,3R,4R,5R)-3,4-(isopropylidenedioxy)-1-[(1R)-1,2-(isopropylidenedioxy)ethyl]-2-oxa-spiro[4.4]non-6-en-8-one, proceeded stereoselectively in some cases affording a variety of β-functionalized cyclopentanone derivatives. The thermal treatment of (1S,3R,4R,5R)-7-(hydroxymethyl)-3,4-(isopropylidenedioxy)-1-[(1R)-1,2-(isopropylidenedioxy)ethyl]-2-oxaspiro[4.4]non-6-ene, another d-glucose-derived spirocyclic substrate, with triethyl orthoacetate in the presence of a catalytic amount of acid afforded the Claisen rearrangement product with a high level of diastereoselectivity.     

Total synthesis of the proposed structures of hyacinthacines C2, C3, and their C5-epimers

Synthesis and structural confirmation of highly oxygenated pyrrolizidine alkaloids, hyacinthacines C₂ [(1S,2R,3R,5R,7S,7aR)-3,5-hydroxymethyl-1,2,7-trihydroxypyrrolizidine], C₃[(1S,2R,3R,5S,7R,7aR)-3,5-hydroxymethyl-1,2,7-trihydroxypyrrolizidine], and their C5-epimers were achieved on the basis of the highly divergent method employing (S)-(−)-2-pyrrolidone-5-carboxylic acid as the starting material.