A divergent and stereoselective approach to phenolic 1,7-dihydroxy-bisabolane sesquiterpenes: asymmetric total synthesis of (+)-curcutetraol, (+)-sydonol, (+)-sydonic acid,and (+)-7-O-methylsydonic acid

The combined use of the Sharpless asymmetric epoxidation, a number of stereospecific chemical transformations, and the 3,5-hexadienoic acid benzannulation protocol allowed us to devise a new, divergent, and stereoselective approach to terpenes with a chiral tertiary hydroxyl group at the ortho-position of a phenol functional group. Accordingly, the natural occurring enantiomeric forms of the bisabolane sesquiterpenes (+)-curcutetraol, (+)-sydonol, (+)-sydonic acid, and (+)-7-O-methylsydonic acid were synthesized with high enantiomeric purity starting from geraniol. The latter two acids were prepared in enantioenriched form for the first time.     

New sesquiterpenes and calebin derivatives from Curcuma longa

One novel sesquiterpene with new skeleton, (6S)-2-methyl-6-(4-hydroxyphenyl-3-methyl)-2-hepten-4-one (1), two new bisabolane sesquiterpenes, (6S)-2-methyl-6-(4-hydroxyphenyl)-2-hepten-4-one (2), (6S)-2-methyl-6-(4-formylphenyl)-2-hepten-4-one (3), and two calebin derivatives, 4'-(4'-hydroxyphenyl-3'-methoxy)-2'-oxo-3'-butenyl-3-(4'-hydroxyphenyl)-propenoate (4) and 4'-(4'-hydroxyphenyl)-2'-oxo-3'-butenyl-3-(4'-hydroxyphenyl-3'-methoxy)-propenoate (5) were isolated along with five known bisabolane sesquiterpenes from Curcuma longa. 1-4 were new compounds and 5 was a new natural product. Their structures were established by spectral methods.     

Stereospecific Synthesis of (−)-β-Turmerone and (−)-Bisacurol

The structure of (+)-β-turmerone ((+)- 1a ), a constituent of the rhizomes of Curcuma longa Linn. , and Curcuma xanthorriza, is established as (1′R,6S)-2-methyl-6-(4′-methylenecyclohex-2′-en-1′-yl)hept-2-en-4-one by synthesis of its enantiomer (−)- 1a , and of the corresponding (1′S,6S)-diastereoisomer (+)- 1b as well. In a stereospecific seventeen-step procedure, the monoterpene diols 2a and 2b of well-established configuration are converted into the target compounds (−)- 1a and (+)- 1b , respectively. Moreover, (−)-bisacurol (−)- 3a (II), the enantiomer of another bisabolane sesquiterpene derived from Curcuma xanthorriza, is obtained as a single stereoisomer and shown to be (1′S,6R)-2-methyl-6-(4′-methylenecyclohex-2′-en-1′-yl)hept-2-en-4-ol, the relative configuration at the remaining OH-substituted chiral center C(4) still being unknown.     

Constituents of south Indian vetiver oils

The essential oils isolated from vetiver [Vetiveria zizanioides (L.) Nash.] roots collected from four locations in south India were analyzed by GC-FID and GC-MS. Eighty constituents, representing 94.5-97.8% of the oils, have been identified. The oils from Bangalore, Hyderabad, Kundapur, and Mettupalayam were rich in sesquiterpenes and oxygenated sesquiterpenes with cedrane, bisabolane, eudesmane, eremophilane, and zizaane skeletons. The main components of the four essential oils were: eudesma-4,6-diene (delta-selinene) + beta-vetispirene (3.9-6.1%), beta-vetivenene (0.9-9.4%), 13-nor-trans-eudesma-4(15),7-dien-11-one + amorph-4-en-10-ol (5.0-6.4%), trans-eudesma-4(15),7-dien-12-ol (vetiselinenol) + (E)-opposita-4(15),7(11)-dien-12-ol (3.7-5.9%), eremophila-1 (10),11-dien-2alpha-ol (nootkatol) + ziza-6(13)-en-12-ol (khusimol) (16.1-19.2%), and eremophila-1(10),7(11)-dien-2alpha-ol (isonootkatol) + (E)-eremophila-1(10),7(11)-12-ol (isovalencenol) (5.6-6.9%). The important compounds that impart the characteristic vetiver odor are: khusimene, delta-selinene, beta-vetivenene, cyclocopacamphan-12-ol (epimers A and B), vetiselinenol, khusimol, isovalencenol, khusimone, alpha-vetivone, and beta-vetivone. The chemical profiles of the oils are comparable to Haitian vetiver oil.     

Sesquiterpenoid constituents of the liverwort Marsupella aquatica

Nine new amorphane sesquiterpenoids, (+)-7β-hydroxyamorpha-4,11-diene, (−)-9α-hydroxyamorpha-4,7(11)-diene, (−)-3α-hydroxyamorpha-4,7(11)-diene, (−)-3α-acetoxyamorpha-4,7(11)-diene, (−)-amorpha-4,7(11)-dien-3-one, (+)-2,8-epoxyamorpha-4,7(11)-diene, (+)-5,9-epoxyamorpha-3,7(11)-diene, (−)-2α-hydroxyamorpha-4,7(11)-diene and (−)-2β-acetoxyamorpha-4,7(11)-diene, were isolated from the essential oil of the liverwort Marsupella aquatica, collected near Gaschurn/Montafon, Austria. The isolated compounds and their chemical transformations were investigated using enantioselective GC and extensive spectroscopic studies (HRMS, ¹H, ¹³C and 2D NMR). The absolute configuration of most of the isolated compounds were established by conversions to known compounds. In addition, ¹H, and ¹³C NMR data of (−)-myltayl-4-ene are reported for the first time.     

Catalytic Enantioselective β-Alkylation of α,β-Unsaturated Aldehydes by Combination of Transition-Metal- and Aminocatalysis: Total Synthesis of Bisabolane Sesquiterpenes

Branching out! The first co-catalytic enantioselective (up to 98:2 e.r.) β-alkylation of α,β-unsaturated aldehydes by combination of simple chiral amine and copper catalysts provides β-branched aldehydes in a one-pot protocol. The methodology was applied to the short total syntheses of bisabolane sesquiterpenes (S)-(+)-curcumene, (E)-(S)-(+)-3-dehydrocurcumene and (S)-(+)-tumerone.     

New Dimeric Monoterpenes and Dimeric Diterpenes from the Heartwood of Chamaecyparis obtusa var. formosana

Two dimeric monoterpenes obtusal A and B, and two dimeric diterpenes obtusanol A and B, along with (−)‐(S)‐citronellol, (−)‐(S)‐citronellic acid, (+)‐borneol, (+)‐sugiol, and (−)‐6,12‐dihydroxyabieta‐5,8,11,13‐tetraen‐7‐one, have been isolated from the heartwood of Chamaecyparis obtusa var. formosana and were characterized by spectroscopic means, including 2D‐NMR techniques and chemical methods. Synthesis of (−)‐obtusal A and (+)‐obtusal B were carried out.     

Efficient Total Synthesis of Racemic Bisabolane Sesquiterpenes Curcuphenol and Xanthorrhizol Starting from Substituted Acetophenones

A total synthesis of natural bisabolane sesquiterpenes curcuphenol ( 1 ) and xanthorrhizol ( 2 ) was developed by using the substituted acetophenones 4 and 5 , respectively, as starting materials. The acetyl group of the latter was activated through ethoxycarbonylation to carry out the prenylation, which was performed successfully to give their respective precursors 11a and 11b , and 21 that were converted into the corresponding natural sesquiterpenes 1 and 2 , respectively, over four steps and in high overall yields.     

A short synthesis of bisabolane sesquiterpenes

A facile total synthesis of three members of the bisabolane sesquiterpene family, namely (±)-curcumene, (±)-xanthorrhizol and (±)-curcuhydroquinone had been achieved in high overall yield. The synthesis used bromobenzene derivatives as starting materials. The halogen-lithium exchange followed by addition of isoprenylacetone and reduction of the obtained carbinols are the key steps of the synthetic pathway. This synthetic approach provides a new route to the bisabolane sesquiterpenes.     

New Epoxy‐Substituted Nitrogenous Bisabolene‐Type Sesquiterpenes from a Hainan Sponge Axinyssa sp.

Two new uncommon epoxy‐substituted nitrogenous bisabolene‐type sesquiterpenes, 3‐formamido‐7,8‐epoxy‐α‐bisabolane ( 4 ), 3‐isocyano‐7,8‐epoxy‐α‐bisabolane ( 5 ), together with three known related sesquiterpenes, 1 – 3 , were isolated from the Hainan sponge Axinyssa sp. Their structures were determined on the basis of extensive spectroscopic analyses and by comparison of their NMR data with those of structurally related compounds.     

The first enantioselective synthesis of (−)-microbiotol and (+)-β-microbiotene

The first enantioselective total synthesis of (−)-microbiotol and (+)-β-microbiotene, sesquiterpenes containing three neighboring quaternary carbon atoms belonging to the cyclocuparane group, starting from cyclogeraniol employing a Sharpless–Katsuki asymmetric epoxidation, a boron trifluoride etherate mediated epoxide rearrangement and an intramolecular diazo ketone cyclopropanation as key steps, is described.     

Higher terpenes from lower terpenes: A short,simple and versatile route to bisabolane sesquiterpenoids

An efficient procedure for the elaboration of abundantly available monoterpenes to bisabolane sesquiterpenes utilising catalysed ene addition as the key reaction is described.     

Synthesis of bisabolane sesquiterpenes: a Johnson-Claisen rearrangement approach

<正>Several bisabolane sesquiterpenes,(±)-curcumene,(±)-curcuphenol,(±)-curcudiol and(±)-curcuhydroquinone,have been synthesized in racemic form and fully characterized.The salient characteristic of our approach is that a Johnson-Claisen arrangement was involved as a key step.     

Enantiodivergent syntheses of cycloheptenone intermediates for guaiane sesquiterpenes

The syntheses of enantiomeric 6-isopropenyl-3-methyl-2-cycloheptenones 16 and 22 have been effected starting from (R)-(−)-carvone. In the synthesis of 16, (R)-(−)-carvone was reduced and the resulting dihydrocarvone transformed regioselectively into silyl enol ethers. Cyclopropanation with dibromocarbene and in situ rearrangement gave an α-bromo-cycloheptenone which was reduced to the (R)-(+)-cycloheptenone 16. In the synthesis of 22, (R)-(−)-carvone was cyclopropanated with a sulfur ylide, followed by reduction with LiAlH₄ and acid-catalyzed cyclopropylcarbinyl rearrangement to afford a cycloheptenol. Oxidation and double bond conjugation led to the (S)-(−)-cycloheptenone 22 in a partially racemized form. Four cycloheptenones have been obtained and are suitable intermediates for the enantiodivergent syntheses of guaiane sesquiterpenes.     

An expedient route for the practical preparation of optically active (−)-gossypol

A simple and practical procedure has been developed for the resolution of racemic gossypol. The commercially available l-amino acid esters have been employed as the resolving agents with the l-tryptophan methyl ester (l-Trp-OMe) as the best reagent of choice. The individual diastereoisomeric gossypol adducts derived from l-Trp-OMe are readily separated by a simple filtration step to give the (−)-diastereoisomeric adduct, and its (+)-diastereoisomeric adduct can be easily obtained by simple evaporation of the mother liquor. Acid hydrolysis of the separated adduct gave (−)-gossypol and (+)-gossypol, respectively, in high chemical yields (quantitatively) and in high enantiomeric excesses (>95%).     

The enantioselective syntheses of bisabolane sesquiterpenes Lepistirone and Cheimonophyllon E

The synthetic approach to the bisabolane sesquiterpenes Lepistirone 1 and Cheimonophyllon E 2 involves the transformation of (+)-2-carene (5) into the p-menthane furans 8 and 11. Regio- and stereoselective alkylation, and standard reactions complete the enantioselective syntheses.     

Bioinspired Transformations Using Strictosidine Aglycones: Divergent Total Syntheses of Monoterpenoid Indole Alkaloids in the Early Stage of Biosynthesis

A series of bioinspired transformations that are applied to convert strictosidine aglycones into monoterpenoid indole alkaloids is reported. The highly reactive key intermediates, strictosidine aglycones, were prepared in situ by simple removal of a silyl protecting group from the silyl ether derivatives, and converted selectively via bioinspired transformations under substrate control into heteroyohimbine- and corynantheine-type, and akagerine and naucleaoral related alkaloids. Thus, concise, divergent total syntheses of 13 monoterpenoid indole alkaloids, (−)-cathenamine, (−)-tetrahydroalstonine, (+)-dihydrocorynantheine, (−)-corynantheidine, (−)-akagerine, (−)-dihydrocycloakagerine, (−)-naucleaoral B, (+)-naucleidinal, (−)-naucleofficines D and III, (−)-nauclefiline, and (−)-naucleamides A and E, were accomplished in fewer than 13 steps.     

Divergent Total Syntheses of 2, 6-Dioxabicyclo[3.3.1]nonan-3-one Styryllactones: (−)-Goniopypyrone, (+)-Goniochelienlactone and (+)-7-Acetylgoniochelienlactone

Stereoselective total syntheses of (+)-goniochelienlactone, (+)-7-acetylgoniochelienlactone and (−)-goniopypyrone were accomplished by divergent strategies starting from readily available chiral pool methyl α-D-mannopyranoside. The present work provided an efficient strategy for the stereoselective construction of highly functionalized dioxabicyclo[3.3.1]nonan-3-one ring system through a sequential Bernet-Vasella-type reductive elimination/nucleophilic addition and a sequential cross-metathesis/intramolecular oxa-Michael addition in a one-pot process.     

Microbial reduction of 2-(6-m-methoxyphenyl-3-oxohexyl)-2,4-dimethylcyclopenta-1,3-dione with Schizosaccharomyces pombe (NRRL Y-164)

A mixture of cis- and trans-2-(6-m-methoxyphenyl-3-oxohexyl)-2,4-dimethylcyclopenta-1,3-dione (±)-10 was synthesized and incubated with Schizosaccharomyces pombe (NRRL Y-164) to give (+)-11, (+)-12, (−)-13, and (−)-14 in 19, 13, 22, and 16% yields, respectively. Chromic acid oxidation of these microbiologically reduced products gave (−)-10a, (+)-10b, (+)-10a, and (−)-10b, respectively.     

Synthesis of disparlure analogues,using resolution on microcrystalline cellulose triacetate-I

The gypsy moth, Lymantria dispar, uses a chiral epoxide, (+)-(7R,8S)-2-methyl-7,8-epoxyoctadecane, (+)-disparlure, as its main sex attractant. The moths can detect both enantiomers of disparlure and respond differently to each one. In an effort to understand the structure–activity relationships of the gypsy moth olfactory system, we prepared the analogues of (+)- and (−)-disparlure. The key intermediate in route to the analogues was 2-epoxytridecan-1-ol. Herein we report the resolution of 2-epoxytridecan-1-yl esters on microcrystalline cellulose triacetate and the synthesis of 5-oxa and (5Z)-ene analogues of (+)- and (−)-disparlure. An effort to make 5-aza analogues resulted in the formation of anti-5-(1-hydroxy-1-undecyl)-3-(3-methylbutyl)oxazolidin-2-one. The analogues were tested for their electroantennogram responses and for their ability to bind to pheromone-binding protein 1 (PBP1). We found that the 5-oxa analogues gave strong responses and that the antenna and the PBP1 no longer distinguish the enantiomers of the 5-oxa analogues. The analogues all bound the PBP1 with similar affinity to (−)-disparlure.