Stereoselective total synthesis of (−)-cleistenolide

A stereoselective total synthesis of (−)-cleistenolide (1) derived from d-(−)-isoascorbic acid has been described. The new synthetic strategy involves highly diastereoselective reduction, one-pot protection of required benzoyl, acetyl groups, and the RCM reaction by using Grubbs catalyst are the key steps with considerable yields.     

The stereoselective total synthesis of (−)-cleistenolide

The stereoselective total synthesis of (−)-cleistenolide is described employing the Barbier allylation, MacMillan α-hydroxylation, Stille-Gennari olefination, and CeCl₃·7H₂O mediated lactonization as key steps.     

Total synthesis of (−)-centrolobine

Stereoselective synthesis of (−)-centrolobine, an anti-Leishmania agent, was accomplished via an intramolecular Barbier-type reaction of iodo-ester with n- or t-butyllithium followed by Lewis acid-promoted Et₃SiH reduction of the resulting hemiacetal.     

Total synthesis of (−)-xanthatin

The first enantioselective total synthesis of xanthatin, a xanthanolide sesquiterpenoid exhibiting potent antibacterial activity against MRSA, has been accomplished from an optically pure bicyclic lactone, previously synthesized by our group.     

Total synthesis of (−)-muricatacin

A total synthesis of (−)-muricatacin has been achieved using a commercially available starting material and our furan approach to oxacyclic systems, the proven scope of which is thus broadened.     

Total synthesis of (−)-incarvilline

An enantioselective synthesis of (−)-incarvilline is presented, employing a three-component coupling reaction and an intramolecular enone-olefin [2+2] photocycloaddition followed by a SmI₂-induced cyclobutane ring-opening reaction.     

Total synthesis of (−)-clavosolide A

The total synthesis of (−)-clavosolide A is achieved employing a radical-mediated route to build the substituted tetrahydropyran unit, a Yamaguchi reaction to construct the diolide aglycon and the Schmidt method for the final glycosidation step.     

Total synthesis of (−)-amathaspiramide F

The stereoselective total synthesis of the marine alkaloid, (−)-amathaspiramide F (1), was achieved from the α-hydroxy-α-ethynylsilane 2. The key steps involved in the synthesis were (1) the enolate Claisen rearrangement of the α-acyloxy-α-alkenylsilane for the stereoselective construction of the consecutive C5 and C9 chiral centers of 1 (erythro configuration), (2) the construction of aza-spirohemiaminal 28, and (3) dibromination during the final stage of the total synthesis. The reaction of the (Z)-α-acyloxy-α-alkenylsilane 22 possessing the Boc-homoallylglycine ester as the acyloxy group underwent stereoselective enolate Claisen rearrangement to give the desired erythro product 23. On the other hand, the reaction of the α-acyloxy-α-alkenylsilane (Z)-5 having Boc-proline gave the unexpected threo product 6. Oxidative cleavage of the vinylsilane group of 23 followed by treatment with heptamethyldisilazane as the methylamine equivalent gave aza-spirohemiaminal 28. The problematic regioselective dibromination to 28 was achieved using n-Bu₄NBrCl₂.     

Total synthesis of (−)-Englerin A

A novel and efficient total synthesis of Englerin A is reported. The synthesis featured an intramolecular olefin metathesis ring closure reaction and a highly stereoselective oxygen bridge formation induced by an iodonium ion. This strategy can be used for the synthesis of natural products Englerin A and Englerin B and can provide flexibility in the preparation of various 9-substituted analogues of Englerin A for further structure–activity relationship studies.     

Total synthesis of (−)-radicamine B

The synthesis of a chiral cyclic nitrone with l-arabino configuration and its application in the total synthesis of radicamine B is reported. An agreement in the spectral data with natural radicamine B but specific rotation with an opposite sign warranted a revision of the absolute configuration of radicamine B.     

Total synthesis of (−)-incarvilline and (−)-incarvillateine

An enantioselective, concise total synthesis of (−)-incarvilline and (−)-incarvillateine has been achieved in longest linear 9 steps (24.3% overall yield) and in 11 steps (16.5% overall yield) from (−)-carvone, respectively. The present synthesis features a notable Favorskii rearrangement of the O-protected chlorohydrin derivative of (−)-carvone to construct four of the five contiguous stereocenters on the bicyclic piperidine moiety and DMAP-catalyzed esterification of incarvilline with α-truxillic acid anhydride to generate incarvillateine skeleton.     

Total synthesis of (−)-petrosiol E

(−)-Petrosiol E, a metabolite of sponge Petrosia strongylata, has been synthesized in 32% overall yield from cheap natural d-xylose in 10 steps. Our strategy provides an efficient way for the total synthesis of other petrosiol members, featuring the three contiguous stereogenic centers are easily constructed from d-xylose chiral template.     

Total synthesis of (−)-martinellic acid

An enantioselective formal total synthesis of the pyrrolo[3,2-c]quinoline natural product martinellic acid has been achieved. The key steps involve a Pd-catalyzed aryl amidation reaction of a pyrroglutamate derivative, an intramolecular [3+2] azomethine ylide-alkene cycloaddition and a reductive ring opening reaction.     

Total synthesis of (−)-baconipyrone C

A highly stereoselective asymmetric total synthesis of marine polypropionate (−)-baconipyrone C has been achieved. Utilization of desymmetrization technique to create five stereogenic centres, Sharpless epoxidation, Gilman's reaction and resolution of methyl group using enzyme PS-C is the highlight of the synthesis.     

Total synthesis of (−)-physovenine from (−)-3a-hydroxyfuroindoline

Total synthesis of calabar bean alkaloid (−)-physovenine (−)-3 has been achieved in a concise manner starting from optically active (−)-3a-hydroxyfuroindoline (−)-2, synthesized via modified Sharpless epoxidation of tryptophol 1. Our strategy involved a stereospecific radical substitution reaction and regioselective oxidation at the C5 position.     

Total synthesis of (+)-epiepoformin and (−)-phyllostine

An efficient asymmetric total synthesis of naturally occurring cyclohexeneoxides, (+)-epiepoformin and (−)-phyllostine has been achieved using the chiral building block available from the base-catalyzed Diels-Alder reaction of 3-hydroxy-2-pyrone. Since (−)-theobroxide was derived from the same precursor of (+)-epiepoformin, the formal total synthesis of (−)-theobroxide has also been achieved.     

Total synthesis of (S)-(−)-cyclooroidin

The first total synthesis of enantiopure (S)-(−)-cyclooroidin is described. Absolute configuration of this natural product has been confirmed by comparison of the optical rotation value of our synthetic sample with the one measured on natural cyclooroidin.     

Total synthesis of (−)-nakadomarin A: alkyne ring-closing metathesis

A 13-step, highly stereoselective synthesis of (−)-nakadomarin A has been achieved using the combination of a bifunctional organocatalyst controlled Michael addition, a nitro-Mannich/lactamization cascade, an alkyne ring-closing metathesis/syn-reduction, and furan/iminium ion cyclization/reduction as key steps.     

Total synthesis of racemic,natural (+) and unnatural (−) scorzocreticin

The first total synthesis of racemic scorzocreticin and its pure enantiomers is described from readily available 3,5-dihydroxybenzoic acid. The key steps include Wittig olefination, asymmetric Me-CBS (Corey–Bakshi–Shibata) oxazaborolidine reduction, and improved Pd-catalyzed intramolecular lactonization reactions. Both the (S)-natural and (R)-unnatural enantiomers of scorzocreticin have been synthesized in excellent enantioselectivities (>99% and 99% ee, respectively). In addition, 1,10-phenanthroline, a bidentate N-ligand was employed in palladium-catalyzed intramolecular carbonylation/lactonization reaction for the construction of 3,4-dihydroisocoumarin ring.     

Asymmetric synthesis of (−)-tetrahydrolipstatin

Attempts toward the asymmetric synthesis of (−)-tetrahydrolipstatin are described. A palladium catalyzed Wacker-type reaction to convert an alkene to a ketone, highly diastereoselective reduction of a β-hydroxy ketone, selective oxidation of a diol, and modular synthesis are the key features of the successful approach.