Stereoselective synthesis of (−)-microcarpalide

A highly convergent and efficient synthesis of (−)-microcarpalide, a 10-membered lactone displaying remarkable microfilament disrupting activity is described. Ring-closing metathesis and Sharpless asymmetric dihydroxylations are the key steps. Our strategy highlights the application of novel hydroxy lactone precursors for the stereoselective synthesis of (−)-microcarpalide.     

A practical enantioselective total synthesis of (−)-(S)-stepholidine

A convergent enantioselective total synthesis of (−)-(S)-stepholidine, a drug candidate for the treatment of schizophrenia and/or drug abuse, was described, which represented the first example of successful auxiliary-assisted Bischler–Napieralski cyclization of amide bearing bromine atom at 2-position of the C ring, followed by an introduction of the aryl methyl ester via Br–Li exchange. (−)-(S)-Stepholidine was synthesized in 6 steps, with 52% overall yield and >99% ee. The reported synthesis is practically free from chromatographic separation.     

Stereoselective formal synthesis of (−)-centrolobine

Stereoselective formal synthesis of (−)-centrolobine was achieved from naturally occurring l-(+)-tartaric acid, employing a facile FeCl₃ mediated stereoselective formation of a tetrahydropyran as the key step.     

Stereoselective synthesis of (−)-tetrahydrolipstatin via a radical cyclization based strategy

An efficient and flexible approach for the total synthesis of (−)-tetrahydrolipstatin is described. The main features of the synthetic strategy are a stereocontrolled radical cyclization and the successful utilization of commercially available S-malic acid.     

Stereoselective synthesis of (−)-microcarpalide

A stereoselective approach for the synthesis of the bio-active decanolactone (−)-microcarpalide was achieved from chiral pool tartaric acid. The synthesis of pivotal intermediates en route to the decanolactone was achieved from α-benzyloxy aldehydes derived from l- and d-tartaric acid.     

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.     

First total synthesis of parvistone C and its C8-epimer

Diastereoselective first total synthesis of parvistone C 1 and C8-epimer 1a are described. The key features of our synthesis include Sharpless asymmetric dihydroxylation, stereoselective aryl Grignard reactions, Still–Gennari olefination, and intramolecular cyclization.     

Enantioselective synthesis of (−)-barrenazines A and B

A short enantioselective synthesis of barrenazines A and B is described. Barrenazines A and B are prepared following a common synthetic route in nine steps (19% overall yield) and eight steps (21% overall yield), respectively, from readily available 4-methoxy-3-(triisopropylsilyl)pyridine. The synthesis relies on a highly diastereoselective nucleophilic addition of a Grignard reagent to a chiral acylpyridinium salt, a radical azidation of a silyl enol ether and the assembly of the pyrazine ring by reductive dimerization of a functionalized 5-azidopiperidin-4-one.     

Stereoselective synthesis of tetrahydroisoquinoline alkaloids: (−)-trolline, (+)-crispin A, (+)-oleracein E

Tetrahydroisoquinoline alkaloids, (S)-(−)-trolline, (R)-(+)-crispin A, and (R)-(+)-oleracein E, have been synthesized stereoselectively from the both enantiomers of common intermediate (S)-4 and (R)-4. The key step in the synthesis include a stereoselective Bi(OTf)₃-catalyzed intramolecular 1,3-chirality transfer reaction of chiral non-racemic amino allylic alcohols (S)-6 and (R)-6 to construct both enantiomers of (E)-1-propenyl tetrahydroisoquinoline 4.     

A total synthesis of (+)-preussin and its 5-epimer

(+)-Preussin (1) and its 5-epimer were synthesized from the divmylcarbmol (3) with Sharpless asymmetric epoxidation of 3 and the oxidative cyclization of 9 with PDC as the key steps     

Consecutive sigmatropic rearrangements in the enantioselective total synthesis of (−)-joubertinamine and (−)-mesembrine

Joubertinamine and mesembrine are two related alkaloids isolated from Sceletium plants. From the perspective of chemical synthesis, the major challenge posed by joubertinamine and mesembrine is undoubtedly the construction of the benzylic quaternary stereogenic center. We became intrigued by the prospect of applying successive sigmatropic rearrangements to build the key structural features of these alkaloids in enantioselective manner. In this article, we detail our results in this area, which include the enantioselective total synthesis of (−)-joubertinamine and (−)-mesembrine.     

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.     

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.     

Enantioselective synthesis of (−)-idiospermuline

The enantioselective total synthesis of the nonacyclic polypyrrolidinoindoline (−)-idiospermuline is described. Stereocontrolled formation of the vicinal quaternary carbon centers is achieved in a single step by dialkylation of an unsymmetrical prostereogenic dienolate with a tartrate-derived chiral dielectrophile. A catalyst-controlled diastereoselective Heck cyclization is employed to form the diaryl-substituted quaternary center.     

An efficient total synthesis of (−)-anamarine

An efficient synthesis of (−)-anamarine is described using d(+)-mannitol and (R)-epichlorohydrin. The synthesis is achieved starting from easily accessible d(+)-mannitol using a selective benzoylation, regioselective epoxide ring opening, a selective acetonide deprotection, tosylation and cross metathesis reaction.     

Stereoselective synthesis of (+)-(8R,8aR)-perhydro-8-indolizidinol

A highly stereoselective total synthesis of (+)-(8R,8aR)-perhydro-8-indolizidinol is described. Key steps involved in this synthesis are diastereoselective zinc allylation, azido-olefin cyclization and reductive amination followed by cyclization which effectively constructed the indolizidine ring. This contributes a unique approach to the synthesis of indolizidine alkaloids that offers the advantages of brevity and relatively high overall yields.     

Stereocontrolled synthesis of piperidine alkaloids, (−)-241D and (−)-isosolenopsin

Highly diastereocontrolled synthesis of alkaloids, (−)-241D and (−)-isosolenopsin was achieved in 7.7% and 5.3% yields, respectively, using a Barbier-type allylation of a chiral imine and d-proline catalyzed aldol addition reaction of a β-amino aldehyde with acetone as the key steps. The synthesis involves a nine-step sequence using (S)-valinate imine in a Barbier-type allylation for the first time.     

A stereoselective total synthesis of (−)-andrachcinidine via an olefin cross-metathesis protocol

A stereoselective total synthesis of 1-(2S,6R)-6-[(2S)-2-hydroxypentyl]-hexahydro-2-pyridinylacetone, (−)-andrachcinidine is reported. The strategy utilizes olefin cross-metathesis and intramolecular S_N2 cyclization as the key steps.     

Stereoselective synthesis of (−)-jimenezin

Total synthesis of jimenezin was achieved via radical cyclization of β-alkoxyacrylate and β-alkoxyvinyl sulfoxide intermediates and intramolecular olefin metathesis reaction.     

Stereoselective synthesis of Nuphar quinolizidine alkaloid, (−)-deoxynupharidine

A stereoselective synthetic route to Nuphar quinolizidine alkaloid, (−)-deoxynupharidine, was established by employing reductive carbon-nitrogen bond cleavage, followed by simultaneous recyclization of a proline derivative with samarium diiodide, and an intramolecular ring-closing metathesis, as the key steps.