1,3‐Oxathiolanes from the Reaction of Aromatic and Enolized Thioketones with Monosubstituted Oxiranes

The reactions of 4,4′‐dimethoxythiobenzophenone ( 1 ) with (S)‐2‐methyloxirane ((S)‐ 2 ) and (R)‐2‐phenyloxirane ((R)‐ 6 ) in the presence of a Lewis acid such as BF₃?Et₂O, ZnCl₂, or SiO₂ in dry CH₂Cl₂ led to the corresponding 1 : 1 adducts, i.e., 1,3‐oxathiolanes (S)‐ 3 with Me at C(5), and (S)‐ 7 and (R)‐ 8 with Ph at C(4) and C(5), respectively. A 1 : 2 adduct, 1,3,6‐dioxathiocane (4S,8S)‐ 4 and 1,3‐dioxolane (S)‐ 9 , respectively, were formed as minor products (Schemes 3 and 5, Tables 1 and 2). Treatment of the 1 : 1 adduct (S)‐ 3 with (S)‐ 2 and BF₃?Et₂O gave the 1 : 2 adduct (4S,8S)‐ 4 (Scheme 4). In the case of the enolized thioketone 1,3‐diphenylprop‐1‐ene‐2‐thiol ( 10 ) with (S)‐ 2 and (R)‐ 6 in the presence of SiO₂, the enesulfanyl alcohols (1′Z,2S)‐ 11 and (1′E,2S)‐ 11 , and (1′Z,2S)‐ 13 , (1′E,2S)‐ 13 , (1′Z,1R)‐ 15 , and (1′E,1R)‐ 15 , respectively, as well as a 1,3‐oxathiolane (S)‐ 14 were formed (Schemes 6 and 8). In the presence of HCl, the enesulfanyl alcohols (1′Z,2S)‐ 11 , (1′Z,2S)‐ 13 , (1′E,2S)‐ 13 , (1′Z,1R)‐ 15 , and (1′E,1R)‐ 15 cyclize to give the corresponding 1,3‐oxathiolanes (S)‐ 12 , (S)‐ 14 , and (R)‐ 16 , respectively (Schemes 7, 9, and 10). The structures of (1′E,2S)‐ 11 , (S)‐ 12 , and (S)‐ 14 were confirmed by X‐ray crystallography (Figs. 1–3). These results show that 1,3‐oxathiolanes can be prepared directly via the Lewis acid‐catalyzed reactions of oxiranes with non‐enolizable thioketones, and also in two steps with enolized thioketones. The nucleophilic attack of the thiocarbonyl or enesulfanyl S‐atom at the Lewis acid‐complexed oxirane ring proceeds with high regio‐ and stereoselectivity via an S_n 2‐type mechanism.     

(E/Z)‐Isomerization of 3′‐Epilutein

3′‐Epilutein (=(all‐E,3R,3′S,6′R)‐4′,5′‐didehydro‐5′,6′‐dihydro‐β,β‐carotene‐3,3′‐diol; 1 ), isolated from the flowers of Caltha palustris, was submitted to both thermal isomerization and I₂‐catalyzed photoisomerization. The structures of the main products (9Z)‐ 1 , (9′Z)‐ 1 , (13Z)‐ 1 , (13′Z)‐ 1 , (15Z)‐ 1 , and (9Z,9′Z)‐ 1 were determined based on UV/VIS, CD, ¹H‐NMR, and MS data.     

Preparation and (E/Z)‐Isomerization of the Diastereoisomers of Violaxanthin

Violaxanthin A (=(all‐E,3S,5S,6R,3′S,5′S,6′R)‐5,6 : 5′,6′‐diepoxy‐5,6,5′,6′‐tetrahydro‐β,β‐carotene‐3,3′‐diol =syn,syn‐violaxanthin; 5 ) and violaxanthin B (=(all‐E,3S,5S,6R,3′S,5′R,6′S)‐5,6 : 5′,6′‐diepoxy‐5,6,5′,6′‐tetrahydro‐β,β‐carotene‐3,3′‐diol=syn,anti‐violaxanthin; 6 ) were prepared by epoxidation of zeaxanthin diacetate ( 1 ) with monoperphthalic acid. Violaxanthins 5 and 6 were submitted to thermal isomerization and I₂‐catalyzed photoisomerization. The structure of the main products, i.e., (9Z)‐ 5 , (13Z)‐ 5 , (9Z)‐ 6 , (9′Z)‐ 6 , (13Z)‐ 6 , and (13′Z)‐ 6 , was determined by their UV/VIS, CD, ¹H‐NMR, ¹³C‐NMR, and mass spectra.     

New Nonhydrolyzable Mimetics of Sialyl Lewis X and Their Binding Affinity to P‐Selectin

Wittig olefination of (2S,3R,5S,6R)‐5‐(acetyloxy)‐tetrahydro‐6‐[(methoxymethoxy)methyl]‐3‐(phenylthio)‐ 2H‐pyran‐2‐acetaldehyde ((+)‐ 10 ) with {2‐[(2S,3R,4R,5R,6S)‐tetrahydro‐3,4,5‐tris(methoxymethoxy)‐6‐methyl‐ 2H‐pyran‐2‐yl]ethyl}triphenylphosphonium iodide ((?)‐ 11 ) gave a (Z)‐alkene derivative (+)‐ 12 that was converted into (αR,2R,3S,4R,5R,6S)‐tetrahydro‐α,3‐dihydroxy‐2‐(hydroxymethyl)‐5‐(phenylthio)‐6‐{(2Z)‐4‐[(2S,3S,4R,5S,6S)‐tetrahydro‐3,4,5‐trihydroxy‐6‐methyl‐2H‐pyran‐2‐yl]but‐2‐enyl}2H‐pyran‐4‐acetic acid ( 8 ), (αR,2R,3S,4R,6S)‐tetrahydro‐α,3‐dihydroxy‐2‐(hydroxymethyl)‐6‐{4‐[(2S,3S,4R,5S,6S)‐tetrahydro‐3,4,5‐trihydroxy‐6‐methyl‐2H‐pyran‐2‐yl]butyl}‐2H‐pyran‐4‐acetic acid ( 9 ), and simpler analogues without the hydroxyacetic side chain such as (2S,3S,4R,5S,6S)‐tetrahydro‐6‐methyl‐2‐{(2Z)‐4‐[(2S,3R,5S,6R)‐tetrahydro‐5‐hydroxy‐6‐(hydroxymethyl)‐3‐(phenylthio)‐2H‐pyran‐2‐yl]but‐2‐enyl}‐2H‐pyran‐3,4,5‐triol ( 30 ), (2S,3S,4R,5S,6S)‐tetrahydro‐6‐methyl‐2‐{[(2S,5S,6R)‐tetrahydro‐5‐hydroxy‐6‐(hydroxymethyl)‐2H‐pyran‐2‐yl]butyl}‐2H‐pyran‐3,4,5‐ triol ((?)‐ 41 ) and (2S,3S,4R,5S,6S)‐tetrahydro‐6‐methyl‐2‐{(2Z/E))‐4‐[(2R,5S,6R)‐tetrahydro‐5‐hydroxy‐6‐(hydroxymethyl)‐2H‐pyran‐2‐yl]but‐2‐enyl}‐2H‐pyran‐3,4,5‐triol ( 43 ). The key intermediates (+)‐ 10 and (?)‐ 11 were derived from isolevoglucosenone and from L ‐fucose, respectively. The following IC₅₀ values were measured in a ELISA test for the affinities of sialyl Lewis x tetrasaccharide, 8, 9, 30 , (?)‐ 41 , and 43 toward P‐selectin: 0.7, 2.5–2.8, 7.3–8.0, 5.3–5.9, 5.0–5.2, and 3.4–4.1 mM , respectively.     

(E/Z)‐Isomerization of (all‐E)‐5,6‐Diepikarpoxanthin

(all‐E)‐5,6‐Diepikarpoxanthin (=(all‐E,3S,5S,6S,3′R)‐5,6‐dihydro‐β,β‐carotene‐3,5,6,3′‐tetrol; 1 ) was submitted to thermal isomerization and I₂‐catalyzed photoisomerization. The structures of the main products, i.e. (9Z)‐ ( 2 ), (9′Z)‐ ( 3 ), (13Z)‐ ( 4 ), (13′Z)‐ ( 5 ), and (15Z)‐5,6‐diepikarpoxanthin ( 6 ), were determined by their UV/VIS, CD, ¹H‐NMR, and mass spectra. In addition, (9Z,13′Z)‐ or (13Z,9′Z)‐ ( 7 ), (9Z,9′Z)‐ ( 8 ), and (9Z,13Z)‐ or (9′Z,13′Z)‐5,6‐diepikarpoxanthin ( 9 ) were tentatively identified as minor products of the I₂‐catalyzed photoisomerization.     

Isomerization of (all‐E)‐Cucurbitaxanthin A

Cucurbitaxanthin A (=(all‐E,3S,5R,6R,3′R)‐3,6‐epoxy‐5,6‐dihydro‐β,β‐carotene‐5,3′‐diol; 1 ) was submitted to thermal isomerization and to I₂‐catalysed photoisomerization. The structure of the main reaction products (9Z)‐ ( 2 ), (9′Z)‐ ( 3 ), (13Z)‐ ( 4 ), and (13′Z)‐cucurbitaxanthin A ( 5 ) was determined by their UV/VIS, CD, ¹H‐NMR, and mass spectra.     

Triumfettamide and Triumfettoside Ic,Two Ceramides and Other Secondary Metabolites from the Stems of Wild Triumfetta cordifolia A. Rich. (Tiliaceae)

Two new ceramides, triumfettamide ( 1 ) and triumfettoside Ic ( 2 ), characterized as (2R,6Z)‐2‐hydroxy‐N‐[(2S,3S,4R)‐1,3,4‐trihydroxyhexacosan‐2‐yl]heptadec‐6‐enamide and (2R)‐N‐{(1S,2R,3E,6Z, 9Z,12Z,15Z)‐1‐[(β‐D ‐glucopyranosyloxy)methyl]‐2‐hydroxyheneicosa‐3,6,9,12,15‐pentaen‐1‐yl}‐2‐hydroxytetradecanamide, respectively, were isolated from the stems of Triumfetta cordifolia A. Rich. besides eight known secondary metabolites identified as heptadecanoic acid, β‐sitosterol glucopyranoside, friedelin, lupeol, betulin, maslinic acid, 2‐hydroxyoleanolic acid and the mixture of stigmasterol and β‐sitosterol. Their structures were determined on the basis of spectroscopic methods as well as HR‐MALDI‐FT‐ICR‐MS analysis, chemical transformation, and by comparison of their physical and spectral data with those reported in the literature and with authentic specimens for some known compounds. Five pentacyclic triterpenoids, friedelin, lupeol, betulin, maslinic acid, and 2‐hydroxyoleanolic acid, have been isolated from Triumfetta genus for the first time.     

Asymmetric Total Synthesis of (11R, 12S, 13S, 9Z, 15Z)-9, 12, 13-Trihydroxyoctadeca-9, 15-dienoic Acid,a self-defensive agent against rice-blast disease

The Diels-Alder adduct of furan and 1-cyanovinyl (1′R)-camphanate was converted into methyl [(tert-butyl)-dimethylsilyl 5-deoxy-2, 3-O-isopropylidene-β-L -ribo-hexofuranosid] uronate ((+)- 4 ). Reduction with diisobutyl-aluminium hydride gave the corresponding aldehyde which was condensed with the ylide derived from triphenyl-(propyl)phosphonium bromide to give (1R, 2S, 3S, 4S)-1-[(tert-butyl)dimethylsilyloxy]tetrahedro-2, 3-(isopropyl-idenedioxy)-4-[(Z)-pent-2′ -enyl]furan ((+)- 7 ). Removal of the silyl protective group gave a mixture of the corresponding furanose that underwent Wittig reaction with the ylide derived from [8-(methoxycarbonyl)-octyl]triphenylphosphonium bromide to yield methyl (11R, 12S, 13S, 9Z, 15Z)-13-hydroxy-11, 12-(isopropylidene-dioxy)octadeca-9, 15-dienoate ((?)- 9 ). Acidic hydrolysis, then saponification afforded (11R, 12S, 13S, 9Z, 15Z)-11, 12, 13-trihydroxyoctadeca-9, 15-dienoic acid ( 1 ).     

Enantioselective Synthesis of 2‐(2‐Arylcyclopropyl)glycines: Conformationally Restricted Homophenylalanine Analogs

Starting from simple aromatic aldehydes and acetylfuran, (E)‐1‐(furan‐2‐yl)‐3‐arylprop‐2‐en‐1‐ones ( 2 ) were synthesized in high yields. Cyclopropanation of the C?C bond with trimethylsulfoxonium iodide (Me₃SO⁺I^?) furnished (furan‐2‐yl)(2‐arylcyclopropyl)methanones 3 in 90–97% yields. Selective conversion of cyclopropyl ketones to their (E)‐ and (Z)‐oxime ethers 5 and oxazaborolidine‐catalyzed stereoselective reduction of the C?N bond followed by separation of the formed diastereoisomers, furnished (2‐arylcyclopropyl)(furan‐2‐yl)methanamines 6 in optically pure form and high yield. Oxidation of the furan ring of (S,S,S)‐, (S,R,R)‐, (R,S,S)‐, and (R,R,R)‐ 6a afforded the four stereoisomers of α‐(2‐phenylcyclopropyl) glycine ( 1a ).     

New Lignan,Benzofuran, and Sesquiterpene Derivatives from the Roots of Leontopodium alpinum and L. leontopodioides

Three new compounds, including a benzofuran, 1‐{(2R*,3S*)‐3‐(β‐D ‐glucopyranosyloxy)‐2,3‐dihydro‐2‐[1‐(hydroxymethyl)vinyl]‐1‐benzofuran‐5‐yl}ethanone ( 1 ), a lignan, [(2S,3R,4R)‐4‐(3,4‐dimethoxybenzyl)‐2‐(3,4‐dimethoxyphenyl)tetrahydrofuran‐3‐yl]methyl (2E)‐2‐methylbut‐2‐enoate ( 2 ), and a silphiperfolene‐type sesquiterpene, [(1S,2Z,3aS,5aS,6R,8aR)‐1,3a,4,5,5a,6,7,8‐octahydro‐1,3a,6‐trimethylcyclopenta[c]pentalen‐2‐yl]methyl acetate ( 3 ), together with the known coumarins obliquin ( 4 ) and its 5‐methoxy derivative 5 were isolated from the roots of Leontopodium alpinum. Another known coumarin derivative, 5‐hydroxyobliquin ( 6 ), was isolated from the roots of L. leontopodioides. The structures of these compounds were established by spectroscopic studies.     

Neoclerodane Diterpenes from Amoora stellato‐squamosa

From the twigs of Amoora stellato‐squamosa, five new neoclerodane diterpenes have been isolated and characterized, methyl (13E)‐2‐oxoneocleroda‐3,13‐dien‐15‐oate (=methyl (2E)‐3‐methyl‐5‐[(1S,2R,4aR,8aR)‐1,2,3,4,4a,7,8,8a‐octahydro‐1,2,4a,5‐tetramethyl‐7‐oxo‐naphthalen‐1‐yl]pent‐2‐enoate; 1 ), (13E)‐2‐oxoneocleroda‐3,13‐dien‐15‐ol (=(4aR,7R,8S,8aR)‐1,2,4a,5,6,7,8,8a‐octahydro‐8‐[(E)‐5‐hydroxy‐3‐methylpent‐3‐enyl]‐4,4a,7,8‐tetramethylnaphthalen‐2(1H)‐one; 2 ), (3α,4β,13E)‐neoclerod‐13‐ene‐3,4,15‐triol (=(1R,2R,4aR, 5S,6R,8aR)‐decahydro‐5‐[(E)‐5‐hydroxy‐3‐methylpent‐3‐enyl]‐1,5,6,8a‐tetramethylnaphthalene‐1,2‐diol; 3 ), (3α,4β,13E)‐4‐ethoxyneoclerod‐13‐ene‐3,15‐diol (=(1R,2R,4aR,5S,6R,8aR)‐1‐ethoxydecahydro‐5‐[(E)‐5‐hydroxy‐3‐methylpent‐3‐enyl]‐1,5,6,8a‐tetramethylnaphthalen‐2‐ol; 4 ), and (3α,4β,14RS)‐neoclerod‐13(16)‐ ene‐3,4,14,15‐tetrol (=(1R,2R,4aR,5S,6R,8aR)‐decahydro‐5‐[3‐(1,2‐dihydroxyethyl)but‐3‐enyl]‐1,5,6,8a‐tetramethylnaphthalene‐1,2‐diol; 5 ), together with two known compounds, (13E)‐neocleroda‐3,13‐diene‐15,18‐diol ( 6 ) and (13S)‐2‐oxoneocleroda‐3,14‐dien‐13‐ol ( 7 ).     

Nine New Sesquiterpenes from Dendrobium nobile

Nine new sesquiterpenes, i.e., dendronobilins A–I ( 1 – 9 ), with copacamphane‐type ( 1 ), picrotoxane‐type ( 2 – 6 ), muurolene‐type ( 7 ), alloaromadendrane‐type ( 8 ), and cyclocopacamphane‐type ( 9 ) skeletons, were isolated from the 60% EtOH extract of the stems of Dendrobium nobile. Their structures were established as (1R,2R,4S,5S,6S,8S,9R)‐2,8‐dihydroxycopacamphan‐15‐one ( 1 ), (2β,3β,4β,5β)‐2,4,11‐trihydroxypicrotoxano‐3(15)‐lactone ( 2 ), (2β,3β,5β,9α,11β)‐2,11‐epoxy‐9,11,13‐trihydroxypicrotoxano‐3(15)‐lactone ( 3 ), (2β,3β,5β,12R*)‐2,11,13‐trihydroxypicrotoxano‐3(15)‐lactone ( 4 ), (2β,3β,5β,12S*)‐2,11,13‐trihydroxypicrotoxano‐3(15)‐lactone ( 5 ), (2β,3β,5β,9α)‐9,10‐cyclo‐2,11,13‐trihydroxypicrotoxano‐3(15)‐lactone ( 6 ), (9β,10α)‐muurol‐4‐ene‐9,10,11‐triol ( 7 ), (10α)‐alloaromadendrane‐10,12,14‐triol ( 8 ), and (5β)‐cyclocopacamphane‐5,12,15‐triol ( 9 ) on the basis of spectroscopic analysis. The absolute configuration of compound 1 was tentatively assigned as (1R,2R,4S,5S,6S,8S,9R) according to its CD spectrum and the octant rule. Compounds 1 and 4 – 9 were inactive in our preliminary in vitro immunomodulatory bioassay.     

(all-E)-12′-Apozeaxanthinol,Persicaxanthine und Persicachrome

( all-E)-12′-Apozeanthinol, Persicaxanthine, and Persicachromes Reexamination of the so-called ‘persicaxanthins’ and ‘persicachromes’, the fluorescent and polar C₂₅-apocarotenols from the flesh of cling peaches, led to the identification of the following components: (3R)-12′-apo-β-carotene-3,12′-diol ( 3 ), (3S,5R,8R, all-E)- and (3S,5R,8S,all-E)-5,8-epoxy-5,8-dihydro-12′-apo-β-carotene-3,12′-diols (4 and 5, resp.), (3S,5R,6S,all-E)-5,6-epoxy-5,6-dihydro-l2′-apo-β-carotene-3,12′-diol =persicaxanthin; ( 6 ), (3S,5R,6S,9Z,13′Z)-5,6-dihydro-12′apo-β-carotene-3,12′-diol ( 7 ; probable structure), (3S,5R,6S,15Z)-5,6-epoxy-5,6-dihydro-12′-apo-β-carotene-3,12′-diol ( 8 ), and (3S,5R,6S,13Z)-5,6-epoxy-5,6-dihydro-12′-apo-β-carotene-3,12′-diol ( 9 ). The (Z)-isomers 7 – 9 are very labile and, after HPLC separation, isomerized predominantly to the (all-E)-isomer 6 .     

Synthese von enantiomerenreinen Violaxanthinen und verwandten Verbindungen

Syntheses of Enantiomerically Pure Violaxanthins and Related Compounds The epoxides 16 and ent- 16 , prepared by Sharpless-Katsuki oxidation of 15 in excellent yield and very high enantiomeric purity, were used as synthons for the preparation of (+)-(S)-didehydrovomifoliol (45) , (+)-(6S, 7E, 9E)-abscisic ester 46 , (+)-(6S, 7E, 9Z)-abscsic ester 47 , (?)-(3S, 7E, 9E)-xanthoxin (49) , (?)-(3R, 7E, 9E)-xanthoxin (50) , (3S, 5R, 6S, 3′S,5′R, 6′S, all-E)-violaxanthin (1) (3R, 5R,6S,3′R,5′R,6′S, all-E)-violaxanthin (55) and their (9Z) (see 53 , 57 ), (13Z) (see 54 , 58 ), and (15Z) (see 60 ) isomers. The novel violadione ( 61 ) was prepared from 1 by oxidation with DMSO/Ac₂O. By base treatment, 61 was converted into violadienedione (62) , a potential precursor of carotenoids with phenolic end groups.     

Bisabolane Derivatives from Leontopodium alpinum

From the roots of Leontopodium alpinum, four new bisabolane sesquiterpenoids, (1R*,2S*,4R*,5S*)‐4‐(acetyloxy)‐2‐[3‐(acetyloxy)‐1,5‐dimethylhex‐4‐enyl]‐5‐methylcyclohexyl (2Z)‐2‐methylbut‐2‐enoate ( 1 ), (1R*,4S*,6R*)‐4‐(acetyloxy)‐6‐[3‐(acetyloxy)‐1,5‐dimethylhex‐4‐enyl]‐3‐methylcyclohex‐2‐en‐1‐yl (2Z)‐2‐methylbut‐2‐enoate ( 2 ), and 3‐methyl‐1‐{2‐[(1R*,2R*,5R*,6S*)‐2,5,6‐tris(acetyloxy)‐4‐methylcyclohex‐3‐en‐1‐yl]propyl}but‐2‐enyl (2Z)‐2‐methylbut‐2‐enoate ( 3 and 4 ) have been isolated. The latter constituents differ from each other by the relative configurations of the chiral centers of the hexenyl side chain.     

Two New Sesquiterpenes from the Roots of Valeriana fauriei Briq.

A phytochemical investigation of the MeOH extract of Valeriana fauriei Briq . roots resulted in the isolation of two new sesquiterpenes, isovalerianin A (=(1β,4Z,6β,8α)‐8‐(acetyloxy)‐1,10‐dihydroxy‐6,11‐cyclogermacr‐4‐en‐15‐al=rel‐(1R,2Z,6S,7R,9R,10S)‐9‐(acetyloxy)‐6,7‐dihydroxy‐7,11,11‐trimethylbicyclo[8.1.0]undec‐2‐ene‐3‐carboxaldehyde; 1 ) and valerianin C (=(2α,3α,6α,8α)‐3‐(acetyloxy)‐2,4,8‐trihydroxyguai‐1(10)‐ene‐12,6‐lactone=rel‐(3R,3aS,4R,7S,8S,9R,9aR,9bR)‐8‐(acetyloxy)‐3a,4,5,7,8,9,9a,9b‐ octahydro‐4,7,9‐trihydroxy‐3,6,9‐trimethylazuleno[4,5‐b]furan‐2(3H)‐one; 2 ), together with six known compounds, i.e., camphor, methyl 4‐hydroxybenzoate, 2‐methoxybenzoic acid, benzoic acid, quercetin, and kaempferol. The structures of the compounds were established by detailed spectral analysis and comparison with previously reported data.     

Rubriflorin A and B,Two Novel Partially Saturated Dibenzocyclooctene Lignans from Schisandra rubriflora

From the stems of Schisandra rubriflora, two novel partially saturated dibenzocyclooctene lignans, named rubriflorin A ( 1 ) and B ( 6 ), as well as the seven known partially saturated dibenzocyclooctene lignans kadsumarin A ( 2 ), kadsurin ( 3 ), heteroclitin B ( 4 ), heteroclitin C ( 5 ), heteroclitin D ( 7 ), interiorin ( 8 ), and interiorin B ( 9 ) were isolated. The structures of the new compounds 1 and 6 were established on the basis of spectral analysis as (5R,6S,7R,8R,13aS)‐8‐(acetyloxy)‐5,6,7,8‐tetrahydro‐1,2,3,13‐tetramethoxy‐6,7‐dimethylbenz([3,4]cycloocta[1,2‐f][1,3]benzodioxol‐5‐yl (2Z)‐2‐methylbut‐2‐enoate and (6R,7R,12aS)‐7,8‐dihydro‐12‐hydroxy‐1,2,3,10,11‐pentamethoxy‐6,7‐dimethyl‐6H‐dibenzo[a,c]cycloocten‐5‐one, respectively.     

Chemical and Cytotoxic Constituents from the Stem of Machilus zuihoensis

Five new compounds, including a novel lactone, machilactone (=rel‐(2R,3aR,6E,6aS)‐2‐heptadecyl‐3a‐methyl‐6‐octadecylidene‐6,6a‐dihydrofuro[2,3‐d][1,3]dioxol‐5(3aH)‐one; 1 ), a new sesquiterpene, 3,4‐dihydroxy‐β‐bisabolol (=rel‐(1R,2S,4R)‐1‐[(1R)‐1,5‐dimethylhex‐4‐enyl]‐1‐methylcyclohexane‐1,2,4‐triol; 2 ), a new secobutyrolactone, methyl (2E)‐2‐(1‐hydroxy‐2‐oxopropyl)eicos‐2‐enoate ( 3 ), two new butyrolactones, machicolide A ( 4 ) and machicolide B ( 5 ) (=3E,4R,5R)‐ and (3Z,4R,5R)‐4,5‐dihydro‐4‐hydroxy‐5‐methoxy‐5‐methyl‐3‐octadecylidenefuran‐2(3H)‐one, resp.) as a mixture, together with known caryophyllene oxide (=4,12,12‐trimethyl‐9‐methylene‐5‐oxatricyclo[8.2.0.0^4,6]dodecane), hexacosane, tetracosanoic acid, isomahubanolide‐23 (=(3E,4R)‐4,5‐dihydro‐4‐hydroxy‐5‐methylidene‐3‐octadecylidenefuran‐2(3H)‐one), and β‐bisabolol (=(1S)‐1‐[(1S)‐1,5‐dimethylhex‐4‐enyl]‐4‐methylcyclohex‐3‐en‐1‐ol) were isolated from the stem wood of Machilus zuihoensis. The structures of these compounds were established by spectroscopic studies. The eicos‐2‐enoate ( 3 ) and β‐bisabolol exhibited marginal cytotoxicity against NUGC and HONE‐1 cancer cell lines in vitro.     

One‐Pot,Asymmetric and Diastereoselective Four‐Component Synthesis of Polyfunctional (Z)‐Alkenyl Methyl Sulfones with Three Stereogenic Centers

The reaction of 1‐(trimethylsilyloxy)cyclopentene ( 9 ) with (±)‐1,3,5‐triisopropyl‐2‐(1‐(RS)‐{[(1E)‐2‐methylpenta‐1,3‐dienyl]oxy}ethyl)benzene ((±)‐ 4a ) in SO₂/CH₂Cl₂ containing (CF₃SO₂)₂NH, followed by treatment with Bu₄NF and MeI gave a 3.0 : 1 mixture of (±)‐(2RS)‐2{(1RS,2Z,4SR)‐2‐methyl‐4‐(methylsulfonyl)‐1‐[(RS)‐1‐(2,4,6‐triisopropylphenyl)ethoxy]pent‐2‐en‐1‐yl}cyclopentanone ((±)‐ 10 ) and (±)‐(2RS)‐2‐{(1RS,2Z)‐2‐methyl‐4‐[(SR)‐methylsulfonyl]‐1‐[(SR)‐1‐(2,4,6‐triisopropylphenyl)ethoxy]pent‐2‐en‐1‐yl}cyclopentanone ((±)‐ 11 ). Similarly, enantiomerically pure dienyl ether (−)‐(1S)‐ 4a reacted with 1‐(trimethylsilyloxy)cyclohexene ( 12 ) to give a 14.1 : 1 mixture of (−)‐(2S)‐2‐{(1S,2Z,4R)‐2‐methyl‐4‐(methylsulfonyl)‐1‐[(S)‐1‐(2,4,6‐triisopropylphenyl)ethoxy]pent‐2‐enyl}cyclohexanone ((−)‐ 13a ) and its diastereoisomer 14a with (1S,2R,4R) or (1R,2S,4S) configuration. Structures of (±)‐ 10 , (±)‐ 11 , and (−)‐ 13a were established by single‐crystal X‐ray crystallography. Poor diastereoselectivities were observed with the (E,E)‐2‐methylpenta‐1,3‐diene‐1‐ylethers (+)‐ 4b and (−)‐ 4c bearing ( 1 S )‐1‐phenylethyl and (1S)‐1‐(pentafluorophenyl)ethyl groups instead of the Greene's auxiliary ((1S)‐(2,4,6‐triisopropylphenyl)ethyl group). The results demonstrate that high α/β‐syn and asymmetric induction (due to the chiral auxiliary) can be obtained in the four‐component syntheses of the β‐alkoxy ketones. The method generates enantiomerically pure polyfunctional methyl sulfones bearing three chiral centers on C‐atoms and one (Z)‐alkene moiety.     

Metabolism of Deuterated threo‐Dihydroxy Fatty Acids in Saccharomyces cerevisiae: Enantioselective Formation and Characterization of Hydroxylactones and γ‐Lactones

Biotransformation of (±)‐threo‐7,8‐dihydroxy(7,8‐²H₂)tetradecanoic acids (threo‐(7,8‐²H₂)‐ 3 ) in Saccharomyces cerevisiae afforded 5,6‐dihydroxy(5,6‐²H₂)dodecanoic acids (threo‐(5,6‐²H₂)‐ 4 ), which were converted to (5S,6S)‐6‐hydroxy(5,6‐²H₂)dodecano‐5‐lactone ((5S,6S)‐(5,6‐²H₂)‐ 7 ) with 80% e.e. and (5S,6S)‐5‐hydroxy(5,6‐²H₂)dodecano‐6‐lactone ((5S,6S)‐5,6‐²H₂)‐ 8 ). Further β‐oxidation of threo‐(5,6‐²H₂)‐ 4 yielded 3,4‐dihydroxy(3,4‐²H₂)decanoic acids (threo‐(3,4‐²H₂)‐ 5 ), which were converted to (3R,4R)‐3‐hydroxy(3,4‐²H₂)decano‐4‐lactone ((3R,4R)‐ 9 ) with 44% e.e. and converted to ²H‐labeled decano‐4‐lactones ((4R)‐(3‐²H₁)‐ and (4R)‐(2,3‐²H₂)‐ 6 ) with 96% e.e. These results were confirmed by experiments in which (±)‐threo‐3,4‐dihydroxy(3,4‐²H₂)decanoic acids (threo‐(3,4‐²H₂)‐ 5 ) were incubated with yeast. From incubations of methyl (5S,6S)‐ and (5R,6R)‐5,6‐dihydroxy(5,6‐²H₂)dodecanoates ((5S,6S)‐ and (5R,6R)‐(5,6‐²H₂)‐ 4a ), the (5S,6S)‐enantiomer was identified as the precursor of (4R)‐(3‐²H₁)‐ and (2,3‐²H₂)‐ 6 ). Therefore, (4R)‐ 6 is synthesized from (3S,4S)‐ 5 by an oxidation/keto acid reduction pathway involving hydrogen transfer from C(4) to C(2). In an analogous experiment, methyl (9S,10S)‐9,10‐dihydroxyoctadecanoate ((9S,10S)‐ 10a ) was metabolized to (3S,4S)‐3,4‐dihydroxydodecanoic acid ((3S,4S)‐ 15 ) and converted to (4R)‐dodecano‐4‐lactone ((4R)‐ 18 ).