Stereoselective Synthesis of Isomers of the Naturally Occurring 13-Hydroxy-2,4,9-tetradecatrienoic Acid. Part II [1]

The stereoselective syntheses of four unsaturated hydroxy fatty acids 13S,2E,4E,9E)- 13-hydroxy-2,4,9-tetradecatrienoic acid, (13S,9Z,11E)-13-hydroxy-9,11-tetradecadienoic acid, (13S,9E, 11E)-13-hydroxy-9,11-tetradecadienoic acid, and (13S,2E,4E,9E)-13-hydroxy-2,4,9,11-tetradecatrienoic acid, are described. Wittig reactions, regioselective oxidation of dialcohol 3, and diastereomerization were used.     

A new dihydrobenzofuran lignan and potential α-glucosidase inhibitory activity of isolated compounds from Mitrephora teysmannii

A new dihydrobenzofuran lignan, (2R,3S)-2-(3′,4′-dimethoxyphenyl)-5-(3-hydroxypropyl)-7-methoxy-2,3-dihydrobenzofuran-3-methyl acetate, named as mitredrusin (1), was isolated from the leaves of Mitrephora teysmannii (Annonaceae) together with 12 known compounds including a related dihydrobenzofuran lignan: (?)-3′,4-di-O-methylcedrusin (2), four polyacetylenic acids: 13(E)-octadecene-9,11-diynoic acid (3), 13(E),17-octadecadiene-9,11-diynoic acid (4), octadeca-9,11,13-triynoic acid (5) and octadeca-17-en-9,11,13-triynoic acid (6), five lignans: (?)-eudesmin (7), (?)-epieudesmin (8), (?)-phillygenin (9), magnone A (10) and forsythialan B (11) and two megastigmans: (3S,5R,6S,7E,9R)-7-megastigmene-3,6,9-triol (12) and annoionol A (13). The chemical structures of these compounds were established on the basis of their 1-D and 2-D NMR spectroscopic data. All compounds were evaluated for their α-glucosidase inhibitory activity. Among these isolates, polyacetylenic acids 3 and 4 showed more than 20-fold much higher activity compared with that of the antidiabetic drug acarbose.     

A new alkaloid from Portulaca oleracea L. and its antiacetylcholinesterase activity

A new alkaloid, (10E, 12E)-9-ureidooctadeca-10, 12-dienoic acid, named oleraurea (1) and 10 known compounds, p-hydroxybenzaldehyde (2), p-hydroxybenzoic acid (3), p-hydroxyacetophenone (4), benzamide (5), (E)-p-coumaramide (6), (E)-ferulamide (7), soyalkaloid A (8), β-carboline-3-carboxylic acid (9), 2, 3, 4, 9-tetrahydro-1H-pyrido [3, 4-b] indole-3-carboxylic acid (10), (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-β-carboline-3-carboxylic acid (11) were obtained from Portulaca oleracea L., in which, compounds 4, 5, 8–11 were isolated from the plant for the first time. The structure of the compound 1 was identified using spectroscopic methods including 1D and 2D NMR, HR-ESI-TOF-MS. The compounds 1, 5–11 presented anticholinesterase activities, but the P. oleracea extract (POE) presented very low anticholinesterase activity.     

Novel Trinor-eremophilanes (Dendryphiellin B,C, and D), Eremophilanes (Dendryphiellin E,F, and G), and Branched C9-Carboxylic Acids (Dendryphiellic Acid A and B) from the Marine Deuteromycete Dendryphiella salina (SUTHERLAND) PUGHet NICOT

Further investigation of global extracts from cultures of the marine deuteromycete Dendryphiella salina leads to the isolation of three novel trinor-eremophilanes esterified by branched C₉-carboxylic acids, dendryphiellin B (= (+)-(1R*,2S*,7R*,8aR*)-1,2,6,7,8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6R*, 2E, 4E)-6-hydroxy-6-methylocta-2,4-dienoate; (+)- 2 ), dendryphiellin C (=(+)-(1R*, 2S*, 7R*, 8aR*)-1,2,6,7,8,8a-hexa-hydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6S, 2E, 4E)-6-methylocta-2,4-dienoate; (+)- 3 )), and dendryphiellin D (=(+)-(1R*, 2S*, 7R*, 8aR*)-1,2,6,7(8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6R*,2E,4E)-6-(hydroxymethyl)octa-2,4-dienoate; (+)- 4 ). An intact eremophilane, dendryphiellin E ( 5 ), and its ethanolysis product dendryphiellin F whose absolute configuration is represented by structural formula (+)- 6 are also isolated from the above extracts. Dendryphiellin E exists as an open form 5a in equilibrium with a closed form 5b . A similar equilibrium exists between the open form 8a and the closed form 8b of a non-esterified eremophilane, dendryphiellin G ( 8 ), which is isolated too from the above extracts and proves structurally related to the cyclic portion of 5 . Finally, the free, branched C₉-carboxylic acids dendryphiellic acid A ((+)- 9 ) and B ((+)- 10 ) which correspond to side chains of the above esterified terpenes are also isolated from the above extracts.     

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 ).     

Leiopathic Acid,a Novel Optically Active Hydroxydocosapentaenoic Acid,and related compounds,from the black coral Leiopathes sp. of Saint Paul Island (S. Indian Ocean)

The antipatharian Leiopathes sp., collected around Saint Paul Island, is shown here to contain, in relatively high amounts, the novel fatty acid leiopathic acid ( = (+)-(10R,7Z,11E,13Z,16Z,19Z)-10-hydroxy-7,11,13,16,19-docosapentaenoic acid; (+)- 1 ), besides (+)-(8R,5Z,9E,11Z,14Z,17Z)-8-hydroxy-5,9,11,14,17-icosapentaenoic acid ((+)- 11 ) and (+)-(8R,5Z,9E,11Z,14Z,)-8-hydroxy-05,9,11,14-icosatetraenoic acid ((+)- 16 ) and their ethyl ester (+)- 2 , (+)- 12 , and (+)- 17 .     

SYNTHESIS OF ANELLATED ANHYDROPYRANOSES ON THE BASIS OF 1,6-ANHYDRO-3-DEOXY-4-METHYLSULFANYL-3-[(METHYLSULFANYL)METHYLENE]-β-D-ERYTHRO-HEXOPYRANOS-2-ULOSE

(Z)-1,6-Anhydro-3-deoxy-4-methylsulfanyl-3-[(methylsulfanyl)methylene]-β-D-erythro-hexopyranos-2-ulose (1) reacted with diethyl malonate, 1,3-diketones, N-aryl-3-oxobutyramides and dialkyl 3-oxoglutarate, respectively, in the presence of potassium carbonate and crown ether to yield diethyl 2-(1,6-anhydro-4-methylsulfanyl—D-arabino-hex-2-ulopyranos-3-ylmethylene) malonate (2), 1-{(1R,2S,8S,9R)-2-hydroxy-4-methyl-8-methylthio-3,11,12- trioxatricyclo7.2.1.0^2,7dodeca-4,6-dien-5-yl} ethanone (3), (1R,2S,12S,13R)-2-hydroxy-12-methylthio-3,15,16-trioxatetracyclo[11.2.1. 0^2,11. 0^4,9] hexadeca- 4(9),10-dien-8-one (4), (1R,8S,9R)-5-acetyl-3-aryl-8-methylthio-11,12-dioxa- 3-azatricyclo-[7.2.1.0^2,7]dodeca-2(7),5-dien-4-ones (5,6) and dialkyl (1R,8S,-9R)-4-hydroxy-8-methylthio-11,12-dioxatricyclo[7.2.1.0^2,7]dodeca-2(7),3,5-triene-3,5-dicarboxylates (7,8), respectively.     

A novel glyceryl ester (glyceryl dendryphiellate A), a trinor-eremophilane (dendryphiellin A1), and eremophilanes (dendryphiellin E1 and E2) from the marine deuteromycete Dendryphiella salina (SUTHERLAND) PUGH et NICOT

Continuing studies of the global extracts from cultures of the marine deuteromycete Dendryphiella salina have led to the isolation of novel compounds that add to the scarce list of marine fungal metabolites. Besides (22E)-ergosta-4.6,8(14),22-tetraen-3-one which, though known from basidiomycetes, was unknown in the sea, they are an unusual glyceryl ester, i.e. glycer-1-yl dendryphiellale A (= (+)-(2R)-2,3-dihydroxyprop-l-yl (6S,2E,4E)6-methylocta-2,4-dienoate; (+)- 1 ), a trinor-eremophilane, i.e. dendryphiellin A1 ( = (+)-(3R*,4E,6E)-7-{[(1R*,2S*,7R*,8aR*)-1,2,6,7,8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2yl]oxycarbonyl}-3-methylhepta-4,6-dienoic acid; (+)- 11 ), and two eremophilanes, i.e. dendryphiellin El ( = (+)-(1R*, 2S*, 7S*,8aR*)-1,2,6,7,8,8a-hexahydro-1,8a-dimethyl-7-(1-methylethenyl)-6-oxonaphthalen-2-yl(6S,2E,4E)-6-methyl-octa-2,4-dienoate; (+)- 13 ) and dendryphiellin E2 ( = (+)-(1R*, 2S*, 8aR*)-1,2,6,7,8,8a-hexahydro-7-isopropyl-idene-1,8a-dimethyl-6-oxonaphthalen-2-yl (6S,2E,4E)-6-Methylocta-2,4-dienoate; (+)- 14 ). Absolute configurations have been established for (+)- 1 via total synthesis and for the acid portion of (+)- 13 and (+)- 14 via transesterification in NaOMe/MeOH which gave in both cases melhyl dendryphiellate A ((+)- 16 ) of known configuration and the free alcoholic moiety of (+)- 14 , i.e. (+)- 17 .     

3,6-Thioanhydro sugar derivatives. An enantiospecific synthesis of (2R,3R,4S)-3-benzyloxy-4-hydroxy-2-[(R)-1-benzyloxy-4-hydroxybutyl]thiolane as the key intermediate for thioswainsonine

Methyl 2-O-benzyl-3,6-thioanhydro-α-D-mannopyranoside ( 9 ) was obtained in eight steps from the commercially available methyl α-D-glucopyranoside. Compound 9 was transformed into (2R,3R,4S)-3-benzyloxy-4-hydroxy-2-[(R)-1-benzyloxy-4-hydroxybutyl]thiolane ( 14 ) by acid hydrolysis of its 2,4-di-O-benzyl derivative 10 followed by reaction of the not isolated 2,4-di-O-benzyl-3,6-thioanhydro-D-mannose ( 11 ) with ethoxycarbonylmethylenetriphenylphosphorane to give an = 1:1 E/Z mixture of the corresponding α,β-unsaturated ester ( 12 ). Finally, catalytic hydrogenation of 12 to ethyl (R)-4-benzyloxy-4-[(2′R)3′R,4′S)-3′-benzyloxy-4′-hydroxythiolan-2′-yl]butanoate ( 13 ) and subsequent reduction with lithium aluminum hydride gave the title compound 14 .     

Novel Sesquiterpenoids from Siegesbeckia orientalis

Five new sesquiterpenoids, namely, 8β‐(angeloyloxy)‐4β,6α,15‐trihydroxy‐14‐oxoguaia‐9,11(13)‐dien‐12‐oic acid 12,6‐lactone ( 1 ), 4β,6α,15‐trihydroxy‐8β‐(isobutyryloxy)‐14‐oxoguaia‐9,11(13)‐dien‐12‐oic acid 12,6‐lactone ( 2 ), 11,12,13‐trinorguai‐6‐ene‐4β,10β‐diol ( 3 ), (1(10)E,4E,8Z)‐8‐(angeloyloxy)‐6α,15‐dihydroxy‐14‐oxogermacra‐(1(10),4,8,11(13)‐tetraen‐12‐oic acid 12,6‐lactone ( 9 ), and (1(10)E,4β)‐8β‐(angeloyloxy)‐6α,14,15‐trihydroxygermacra‐1(10),11(13)‐dien‐12‐oic acid 12,6‐lactone ( 11 ), and three new artifacts, (1(10)E,4Z)‐8β‐(angeloyloxy)‐9α‐ethoxy‐6α,15‐dihydroxy‐14‐oxogermacra‐1(10),4,11(13)‐trien‐12‐oic acid 12,6‐lactone ( 6 ), (1(10)E,4Z)‐8β‐(angeloyloxy)‐9α,13‐diethoxy‐6α,15‐dihydroxy‐14‐oxogermacra‐1(10),4‐dien‐12‐oic acid 12,6‐lactone ( 7 ), and (1(10)E,4Z)‐8β‐(angeloyloxy)‐9α‐ethoxy‐6α,15‐dihydroxy‐13‐methoxy‐14‐oxogermacra‐1(10),4‐dien‐12‐oic acid 12,6‐lactone ( 8 ), together with the three known sesquiterpenoids 4, 5 , and 10 , were isolated from the aerial parts of Siegesbeckia orientalis L. Their structures were established by spectral methods, especially 1D‐ and 2D‐NMR spectral methods.     

Four- and Eight-Carbon Homologation of Benzaldehyde by (1Z,3Z)-Butyltelluro-1,3-Butadiene: Synthesis of Navenone B: Alarm Pheromone of the Mollusk Navanax inermis

Four- and eight-carbon homologation of benzaldehydes is described. The hydrotelluration of (Z)-1-methoxy-but-1-en-3-ynes 1 afforded (1Z,3Z)-1-butyltelluro-4-methoxy-1,3-butadiene 2, this compound 2 underwent a Te/Li exchange reaction, and the butadienyllithium 3 obtained reacted with benzaldehyde to form the corresponding allylic alcohol 4 with total retention of configuration. The allylic alcohol 4a formed underwent acidic hydrolysis, resulting in 5-phenyl-(2E,4E)-dienal 5 (four-carbon homologation of benzaldehyde). Product 5 reacted with the butadienyllithium 3, affording the alcohol 9-phenyl-(1Z,3Z,6E,8E)-1-methoxy-5-hydroxy-nonatetraene 6, which was hydrolyzed or spontaneously transformed into 9-phenyl-(2E,4E,6E,8E)-tetraenal 7, completing the eight-carbon homologation of benzaldehyde. Reaction of 9-phenyl-nona-(2E,4E,6E,8E)-tetraenal 7 with methyllithium in tetrahydrofuran afforded (3E,5E,7E,9E)-10-phenyl-deca-3,5,7,9-tetraen-2-ol 8. The product of the reaction described was employed in the synthesis of (3E,5E,7E,9E)-10-phenyl-deca-3,5,7,9-tetraen-2-one 9, which is known as navenone B, an alarm pheromone of the mollusk Navanax inermis.     

Syntheses of (2R,4'R,8'R)-alpha-tocopherol and (2R,3'E,7'E)-alpha-tocotrienol.

Reaction of trimethyl-hydroquinone with methyl vinyl ketone in acidic methanol gave rac.-2-methoxy-2,5,7,8-tetramethyl-chroman-6-ol ( 8 ). This acetal was converted in four steps to rac.-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-yl)acetic acid ( 13 ). Acid 13 was readily resolved with α-methyl-benzylamine to give the (S)-enantiomer 14 . Treatment of the unwanted (2 R)-isomer with acid regenerated 13 , thus leading to an efficient use of this compound. Employing a side chain derived from phytol, 14 was converted to (2R, 4′R, 8′R)-α-tocopherol ( 1d , ‘natural’ vitamin E). A reaction sequence from 14 involving two highly stereoselective Claisen rearrangements has provided the first total synthesis of (2R,'E,7′E)-α-tocotrienol ( 2d ).     

Isolation,structural elucidation and cytotoxicity evaluation of a new pentahydroxy-pimarane diterpenoid along with other chemical constituents from Aerva lanata

Aervalanata possesses various useful medicinal and pharmaceutical activities. Phytochemical investigation of the plant has now led to the isolation of a new 2α,3α,15,16,19-pentahydroxy pimar-8(14)-ene diterpenoid (1) together with 12 other known compounds identified as β-sitosterol (2), β-sitosterol-3-O-β-D-glucoside (3), canthin-6-one (4), 10-hydroxycanthin-6-one (aervine, 5), 10-methoxycanthin-6-one (methylaervine, 6), β-carboline-1-propionic acid (7), 1-O-β-D-glucopyranosyl-(2S,3R,8E)-2-[(2′R)-2-hydroxylpalmitoylamino]-8-octadecene-1,3-diol (8), 1-O-(β-D-glucopyranosyl)-(2S,3S,4R,8Z)-2-[(2′R)-2′-hydroxytetracosanoylamino]-8(Z)-octadene-1,3,4-triol (9), (2S,3S,4R,10E)-2-[(2′R)-2′-hydroxytetracosanoylamino]-10-octadecene-1,3,4-triol (10), 6′-O-(4″-hydroxy-trans-cinnamoyl)-kaempferol-3-O-β-D-glucopyranoside (tribuloside, 11), 3-cinnamoyltribuloside (12) and sulfonoquinovosyldiacylglyceride (13). Among these, six compounds (8–13) are reported for the first time from this plant. Cytotoxicity evaluation of the compounds against five cancer cell lines (CHO, HepG2, HeLa, A-431 and MCF-7) shows promising IC₅₀ values for compounds 4, 6 and 12.     

Dendryphiellin A,the First Fungal Trinor-eremophilane. Isolation from the marine deuteromycete Dendryphiella salina (SUTHERLAND) PUGHet NICOT

The novel metabolite dendryphiellin A ( = (+)-(1R,2S,8aR)- 1,2,6,7,8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6R*, 2E,4E)-8-hydroxy-6-methylocta-2,4-dienoate; (+)- 1 ) is isolated from cultures of the marine deuteromycete Dendryphiella salina. There is no precedent in fungi for trinor-eremophilanes or for branched C₉ carboxylic acids, the two classes of compounds constituting (+)-1. The structure is secured by NMR spectroscopy and hydrolysis of (+)-1 to give the side-chain moiety ((6R*,2E,4E)-8-hydroxy-6-methylocta-2,4-dienoic acid ( 2 )) intact, whilst the trinor-ermophilane moiety is decomposed. The absolute configuration at the trinor-eremophilane moiety is established from exciton coupling between the dienone and the diene-ester functions.     

A new butanolide from the leaves of <Emphasis Type="Italic">Cinnamomum reticulatum</Emphasis>

A new butanolide, isoreticulide ((4R,3E)-4-hydroxy-5-methylene-3-octadecylidenedihydrofuran-2-one) (1), along with nine compounds including one sesquiterpenoid, (3-methoxy-5H-9,11dioxabenzo[3,4]cyclohepta[1,2-f])inden-7-yl)-methanol (2); six benzenoids, p-hydroxybenzoic acid (3), p-hydroxybenzaldehyde (4), protocatechuic acid (5), ferulic acid (6), trans-methyl p-coumarate (7), and p-dihydrocoumaric acid (8), and two amides, N-trans-feruloyltyramine (9) and dihydroferuloyltyramine (10), were isolated from the leaves of Cinnamomum reticulatum Hayata (Lauraceae). These compounds were characterized and identified by physical and spectral evidence.     

Sarcodictyin A and Sarcodictyin B,Novel Diterpenoidic Alcohols Esterified by (E)-N(1)-Methylurocanic Acid. Isolation from the Mediterranean Stolonifer Sarcodictyon roseum

The Mediterranean stolonifer Sarcodictyon roseum (= Rolandia rosea) (Cnidaria, Anthozoa, Alcyonaria, Stolonifera, Clavulariidae) is shown to contain two novel diterpenoidic alcohols esterified by (E)-N(1)-methyl-urocanic acid (= E)-3-(l-methyl-lH-imidazol-4-yl)acrylic acid). They are sarcodictyin A ( = (?)-(4R,4a,R, 7R,10S,11S,12aR,lZ,5E,8Z)-7,10-epoxy-3,4,4a,7,10,11,12,12a-octahydro-7-hydroxy-6-(methoxycarbonyl)-1,10-dimethyl-4-(1-methylethyl)benzocyclodecen-11-yl (E)-3-(1-methyl-lH-imidazol-4-yl)acrylate; (?)- 1 ) and sarco-dictyin B (the 6-(ethoxycarbonyl analogue; (?)- 2 ). The assignment of the structures is mainly based on 1D- and 2D-NMR data, as well as on chemical transformations of (?)- 1 , such as transesterification with MeONa/MeOH giving methyl (E)-N(1)-methylurocanate ( 3 ) and the free alcohol (+)- 4 and reduction with LiAlH₄ followed by benzoylation giving dibenzoate 7. Absolute configurations are based on Horeau's method of esterification of (+)- 4 .     

Humulene and its derivatives from <Emphasis Type="Italic">Betula pendula</Emphasis> buds

Humulene and its derivatives (6R)-hydroxy-α-humulene [(6R)-hydroxy-(1E,4E,8E)-4,8,11,11tetramethylcycloundeca-1,4,8-triene], (6R)-acetoxy-α-humulene [(6R)-acetoxy-(1E,4E,8E)-4,8,11,11tetramethylcycloundeca-1,4,8-triene], a coumaric acid ester, 14-hydroxy-α-humulene [14-coumaroxy(1E,4E,8E)-4,8,11,11-tetramethylcycloundeca-1,4,8-triene], (1E,6R,8E)-4,5-epoxy-6-hydroxy-4,8,11,11tetramethylcycloundeca-1,8-diene, and (6R,9S)-4,11,11-trimethyl-8-methylene-1,4-cycloundecadien-6,9-diol were observed in the hydrocarbon extract of Betula pendula (Betulaceae) buds. The GC retention indices were determined for all identified compounds.     

Total syntheses of macrosphelides (+)-A, (−)-A and (+)-E

Total syntheses of (+)-macrosphelide A 1 (18.5% overall yield in 11 steps) and (+)-macrosphelide E 2 (23.9% overall yield in 11 steps) have been achieved via the chemoenzymatic reaction product (4R,5S)-4-benzyloxy-5-hydroxy-2(E)-hexenoate 4. The enantiomer (−)-A (1) (14.2% overall yield in 11 steps) of (+)-1 was also synthesized from the chemoenzymatic reaction product (4S,5R)-4-benzyloxy-5-hydroxy-2(E)-hexenoate 4.     

Chiral [2H]-Labelled Methylene Groups in Trienoic- and Dienoic Fatty Acids: A Facile Approach via Asymmetric Epoxidation of [2H] Allyl Alcohols

Chiral [²H] -labelled methylene groups flanked by two double bonds within (poly)unsaturated fatty acids are readily available from trans-2,3-epoxy[2,3-²H₂] alk-4-yn-l-ols, obtained in their turn by asymmetric epoxidation of the corresponding (E)-[2,3-²H₂] alk-2-en-4-yn-l-ols (see Scheme 3). The procedure is exemplified for (8S,3Z,6Z,9Z)-[7,8-²H₂] trideca-3,6,9-trienoic acid ((8S)- 11 ) and (8R)- 11 (Scheme 4) as well as for (5S,3Z,6Z)-[4,5^?2H₂]deca-3,6-dienoic acid ((5S)- 13 ) and (5R)- 13 (Scheme 5).     

5-甲基-[(2E,6E)-3,7,11-三甲基-9-氧代十二碳二烯]苯醌和氢醌的首次全合成

以2-甲基对苯二酚和香叶基溴为起始原料, 经过酚羟基保护, 溴代, Li₂CuCl₄催化的芳基溴与Grignard试剂的偶联以及Julia偶联等一系列反应, 完成了裸鳃亚动物的代谢产物, 5-甲基-[(2E,6E)-3,7,11-三甲基-9-氧代十二碳二烯]苯醌(1)和氢醌(2)的首次全合成, 将1用NaBH₄还原, 得到(±)-3, (±)-3也是此类天然产物之一.