Stereoselective Total Synthesis of the Natural Oxylipin (6R,7E,9R,10S)‐6,9,10‐Trihydroxyoctadec‐7‐enoic Acid

The stereoselective total synthesis of the natural oxylipin, (6R,7E,9R,10S)‐6,9,10‐trihydroxyoctadec‐7‐enoic acid, has been accomplished using nonanal and hexane‐1,6‐diol as the starting materials. The synthesis involves Sharpless kinetic resolution, asymmetric epoxidation, and olefin cross‐metathesis as the key steps.     

The First Stereoselective Total Synthesis of a Naturally Occurring Bioactive Diarylheptanoid, (3R,6E)‐1,7‐Bis(4‐hydroxyphenyl)hept‐6‐en‐3‐ol,through Two Different Approaches

The stereoselective total synthesis of a naturally occurring bioactive diarylheptanoid, (3R,6E)‐1,7‐bis(4‐hydroxyphenyl)hept‐6‐en‐3‐ol, has been accomplished starting from 4‐hydroxybenzaldehyde through two different approaches involving Wittig olefination, hydrolytic kinetic resolution of a racemic epoxide, and olefin cross‐metathesis reaction as the key steps.     

Stereoselective Synthesis of the Non‐Lactonic Portion of (Z)‐Cryptofolione and Approaches towards Its Conversion to (Z)‐Cryptofolione

The stereoselective synthesis of the non‐lactonic part of the natural G₂ checkpoint inhibitor, (Z)‐cryptofolione, has been accomplished. Butane‐1,4‐diol was used as the starting material, and the stereogenic centers were generated through L ‐proline‐catalyzed α‐aminoxylation and Maruoka asymmetric allylation. We attempted to convert this non‐lactonic moiety to (Z)‐cryptofolione via olefin cross‐metathesis reaction, but by this approach another naturally occurring lactonic compound, goniothalamin, was obtained.     

A Concise Total Synthesis of (+)‐(6S,9R,10R)‐Bovidic Acid

A straightforward strategy for the stereoselective synthesis of (+)‐bovidic acid has been developed in eleven steps with an overall yield of 8.85%. The synthesis started from commercially available nonanal, and the key reactions involved were Sharpless asymmetric dihydroxylation, Grignard reaction, and Corey? Bakshi? Shibata reduction.     

The Stereoselective Total Synthesis of (6S)‐5,6‐Dihydro‐6‐[(2R)‐2‐hydroxy‐6‐phenylhexyl]‐2H‐pyran‐2‐one via Prins Cyclization

The stereoselective total synthesis of an antiproliferative and antifungal α‐pyrone natural product (6S)‐5,6‐dihydro‐6‐[(2R)‐2‐hydroxy‐6‐phenylhexyl]‐2H‐pyran‐2‐one is described. The key steps involved are the Prins cyclization, Mitsunobu reaction, and ring‐closing metathesis reaction.     

雌舞毒蛾引诱剂: (＋)-(7R,8S)-7,8-环氧-2-甲基十八烷的不对称全合成

由雌舞毒蛾释放的性引诱剂由于在害虫防治方面的需求不断增加, 已有许多文献对其合成方法进行报道. 以正十一醛和环戊酮为起始原料, 用L-脯氨酸催化的不对称羟醛缩合反应构筑手性中心, 后经拜耶-维利格氧化, 维梯希烯化等步骤, 为雌舞毒蛾性引诱剂(＋)-(7R,8S)-7,8-环氧-2-甲基十八烷提供了一条简便高效的不对称合成新途径, 总收率为37.8%.     

Efficient Synthesis of a Styryl Analogue of (2S,3R,4E)‐N2‐Octadecanoyl‐4‐tetradecasphingenine via Cross‐Metathesis Reaction

The first total synthesis of sphingolipid (2S,3R,4E)‐N²‐octadecanoyl‐4‐tetradecasphingenine ( 1a ), a natural sphingolipid isolated from Bombycis Corpus 101A, and of its styryl analogue 1b was achieved in good overall yield (Schemes 1 and 2). The key step involved the installation with (E) stereoselectivity of a long lipophilic chain or phenyl group on allyl alcohol derivative 3 via a cross‐metathesis reaction (→ 5a or 5b ). The N‐Boc protected 3 was easily accessible from (S)‐Garner aldehyde.     

The Development of a Stereoselective Method for the Synthesis of Tetrasubstituted Derivatives of α,β‐Unsaturated Carboxylic Acids

Alkenes possessing four different carbon‐linked substituents are the main structural motif of many biologically active compounds. The derivatives of (2E)‐3‐(3‐methoxyphenyl)‐2‐methylpent‐2‐enoic acid ((E)‐ 2c ) are suitable precursors for the synthesis of Tapentadol, a novel centrally acting analgesic. It was found that the Ni‐carbometallation reaction of disubstituted alkyne 8 with CO₂ and an Et₂Zn allows for efficient and practical preparation of (E)‐ 2c as a single (E)‐regioisomer in 89% of isolated yield. The influence of the size of the aliphatic substituent of alkyne and the steric hindrance of the organozinc reagent on stereochemical course of the carbometallation reaction was evaluated. Finally, air‐stable Ni(dme)Cl₂ was proposed as an alternative to widely used Ni(cod)₂ catalyst.     

Highly Concise and Stereoselective Total Synthesis of (5R,7S)‐Kurzilactone

A highly concise and stereoselective total synthesis of (5R,7S)‐kurzilactone ( 1 ) was performed by a convergent approach by means of a Jacobsen's hydrolytic kinetic resolution, a Horner? Wadsworth? Emmons reaction for the construction of the α,β‐unsaturated δ‐lactone ring system, and a highly diastereoselective Mukaiyama aldol reaction for the introduction of the formal anti‐1,3‐diol unit (Schemes 2 and 3).     

Modular Total Synthesis of (–)‐Palmyrolide A and (+)‐(5S,7S)‐Palmyrolide A via Ring‐Closing Metathesis and Alkene Isomerization†

A pentamodule assembly approach has been established for total synthesis of the naturally occurring (–)‐palmyrolide A and (+)‐5,7‐epi‐palmyrolide A. By using the racemic tert‐butyl carbinol‐containing alkyl iodide, the two diastereoisomeric macrolides could be obtained from the same sequence of reactions, demonstrating the flexibility of the multimodule assembly strategy for diverted total synthesis.     

Total Synthesis of (−)‐Cleistenolide

An efficient and short total synthesis of (?)‐cleistenolide ( 1 ) from D ‐mannitol with an overall yield of 23.6% is described. The chiron approach for the synthesis of (?)‐cleistenolide involves a one‐C‐atom Wittig olefination, a selective allylic triethylsilyl protection, and a Grubbs‐catalyzed ring‐closure‐metathesis (RCM) reaction as the key steps.     

Stereoselective Synthesis of the C(1) – C(28) Fragment of Amphidinol 3

A stereoselective synthesis of the polyol side chain (C(1) – C(28)) of amphidinol 3 has been accomplished following Sharpless epoxidation, Crimmins aldol reaction, Jacobsen kinetic resolution, Sharpless asymmetric dihydroxylation, and our own reaction for the synthesis of a chiral allylic alcohol from an epoxy alcohol. The olefin functionality was introduced by a cross metathesis and Julia–Kocienski olefination.     

Total synthesis of (3Z,9Z,6S,7R) and (3Z,9Z,6R,7S)-6,7-epoxy-3,9-octadecadienes

(3Z,9Z,6S,7R)-6,7-epoxy-3,9-octadecadiene (1) and (3Z,9Z,6R,7S)-6,7-epoxy-3,9-octadecadiene (2) have been stereoselectively synthesized in eight steps from 2-pentyn-1-ol with an overall yield of 8%. The key steps involved the Sharpless asymmetric dihydroxylation of (2E)-oct-2-en-5-yn-1-ol (6). The new synthetic method is suitable for multigram-scale preparation of 1 and 2 and might be used for producing sufficient quantities of the sex pheromone components for management of the pest of tea plantations.     

Carbohydrate‐Based Studies Toward the Synthesis of Hamigeromycin E: A Stereoselective Total Synthesis of an Isomer of Zeaenol

A stereoselective synthesis of 14‐membered macrolide hamigeromycin E ( 6 ) has been studied by employing ortho‐lithiated formylation, Barbier allylation, Julia–Kocienski olefination, Mitsunobu esterification, and ring‐closing metathesis (RCM) reactions. The final RCM reaction did not provide the target molecule. This study has prompted us to synthesize a stereoisomer of zeaenol and accomplish the total synthesis with the above protocols.     

Stereoselective Total Synthesis of Iso‐Cladospolide B and the 12 Membered‐Macrolactone (6S,12R)‐6‐Hydroxy‐12‐methyloxacyclododecane‐2,5‐dione

Total syntheses of iso‐cladospolide B ( 1 ) and the 12‐membered macrolactone (6S,12R)‐6‐hydroxy‐12‐methyloxacyclododecane‐2,5‐dione ( 2 ), a non‐natural product, were achieved from a common intermediate starting from commercially available 1,9‐nonane diol.     

Stereo‐Inversion in the (4R)‐γ‐Decanolactone Synthesis by Saccharomyces cerevisiae: (2E,4S)‐4‐Hydroxydec‐2‐enoic Acid Acts as a Key Intermediate

Methyl (2E,4R)‐4‐hydroxydec‐2‐enoate, methyl (2E,4S)‐4‐hydroxydec‐2‐enoate, and ethyl (±)‐(2E)‐4‐hydroxy[4‐²H]dec‐2‐enoate were chemically synthesized and incubated in the yeast Saccharomyces cerevisiae. Initial C‐chain elongation of these substrates to C₁₂ and, to a lesser extent, C₁₄ fatty acids was observed, followed by γ‐decanolactone formation. Metabolic conversion of methyl (2E,4R)‐4‐hydroxydec‐2‐enoate and methyl (2E,4S)‐4‐hydroxydec‐2‐enoate both led to (4R)‐γ‐decanolactone with >99% ee and 80% ee, respectively. Biotransformation of ethyl (±)‐(2E)‐4‐hydroxy(4‐²H)dec‐2‐enoate yielded (4R)‐γ‐[²H]decanolactone with 61% of the ²H label maintained and in 90% ee indicating a stereoinversion pathway. Electron‐impact mass spectrometry analysis (Fig. 4) of 4‐hydroxydecanoic acid indicated a partial C(4)→C(2) ²H shift. The formation of erythro‐3,4‐dihydroxydecanoic acid and erythro‐3‐hydroxy‐γ‐decanolactone from methyl (2E,4S)‐4‐hydroxydec‐2‐enoate supports a net inversion to (4R)‐γ‐decanolactone via 4‐oxodecanoic acid. As postulated in a previous work, (2E,4S)‐4‐hydroxydec‐2‐enoic acid was shown to be a key intermediate during (4R)‐γ‐decanolactone formation via degradation of (3S,4S)‐dihydroxy fatty acids and precursors by Saccharomyces cerevisiae.     

Stereoselective Total Synthesis of 4‐Ketoclonostachydiol

An efficient stereoselective total synthesis of the bioactive 14‐membered natural macrocyclic bislactone 4‐ketoclonostachydiol is described. The strategy involves a Jacobsen's hydrolytic kinetic resolution (HKR), epoxide opening, MacMillan α‐hydroxylation, Horner? Wadsworth? Emmons olefination, a Grignard reaction, and Hoveyda? Grubbs‐II‐catalyzed ring‐closing metathesis (RCM) as key steps.     

Synthesis of (E)‐4‐Bromo‐3‐methoxybut‐3‐en‐2‐one,the Key Fragment in the Polyhydroxylated Chain Common to Oscillariolide and Phormidolides A–C

The terminal bromomethoxydiene (BMD) moiety of the polyhydroxylated chain present in phormidolides and oscillariolides has been synthesized for first time. Several strategies for the stereoselective synthesis of the 4‐bromo‐3‐methoxybut‐3‐en‐2‐ones are described. Furthermore, a preliminary study to successfully introduce the BMD within the polyol chain and the fatty acid allowed us to corroborate the end structure of the polyol.