Improved synthesis of C8-C20 segment of pectenotoxin-2

The C8-C20 segment of pectenotoxin-2 was efficiently synthesized in 16% overall yield in 22 steps from l-malic acid via an improved route.     

Enantioselective synthesis of the C10-C20 fragment of fusicoccin A

A synthesis of the fully protected C-ring fragment of the tricyclic diterpene fusicoccin A is reported. The desired cyclopentenyl halides 5a,b are obtained in a total of nine steps. Key transformations of the synthesis sequence are a nonconventional Cr-catalyzed allylic oxidation of a protected intermediate cylcopentenone, a diastereoselective addition of a propenyl Grignard/CeCl(3) reagent to the unmasked cyclopentenone, and an asymmetric hydroboration of the isopropenyl substituent. The protected and suitably functionalized C-ring fragment paves the way to explore further the total synthesis of fusicoccin A.     

Stereoselective synthesis of the C1-C20 segment of the microsclerodermins A and B

An enantioselective route for the synthesis of key fragment C1-C20 resident in microsclerodermins A and B is described. The route features deoxygenative rearrangement of an hydroxy-alkynoate and a highly enantio- and diastereo-controled iterative dihydroxylation as key reactions, starting from S-(−)-citronellol.     

Enantioselective synthesis of the C18-C25 segment of lasonolide A by an oxonia-cope prins cascade

[reaction: see text] A 2-oxonia-Cope Prins cascade was developed that led to a facile and stereoselective synthesis of the C18-C25 segment of lasonolide A. The strategy nicely handles the introduction of the quaternary center in the tetrahydropyran ring, and all of the stereogenic centers in the product arise from a single stereocenter introduced in a catalytic enantioselective reaction.     

Toward the total synthesis of phorboxazole B: an efficient synthesis of the C20-C46 segment

An efficient synthesis of the C20-C46 segment of phorboxazole B is described. The key steps involved Hg(OAc)(2)/I(2)-induced cyclization to construct the cis-tetrahydropyran moiety, the coupling of the metalated 2-methyloxazole 7 with lactone 6, and Julia olefination to furnish the conjugated diene moiety.     

Chemoenzymatic synthesis of the C10-C23 segment of dictyostatin

[reaction: see text] Employing enzymatic desymmetrization and resolution, respectively, the two aldehydes 8 and 20 were prepared. The precursor to aldehyde 8, meso-2,4-dimethylglutaric anhydride 3, could be obtained by base treatment of the diastereomeric mixture. Aldehyde 8 was extended to alkyne 10 by a Marshall reaction introducing four carbon atoms. Lithiation of the derived iodide 15 and trapping of the anion with amide 22 gave ketone 23. This compound led to the C10-C23 fragment 27 of dictyostatin.     

Synthesis of the C8-C20 and C21-C30 segments of pectenotoxin 2

In this study, we synthesized the C8-C20 and C21-C30 segments of the diarrhetic shellfish toxin pectenotoxin 2. The C8-C20 segment was assembled from a phosphonate corresponding to the C8-C15 segment (prepared from l-malic acid in 19 steps) and an aldehyde corresponding to the C16-C20 segment (synthesized from 3-methyl-3-butenol in nine steps) by a twelve-step process including the Horner-Wadsworth-Emmons reaction, regio- and stereoselective reduction of the resulting enone, diastereoselective epoxidation, and 5-exo epoxide cleavage forming the C-ring. The C21-C30 segment was constructed in 13 steps from (S)-glycidol via a route involving E-ring formation by 5-exo epoxide cleavage and stereoselective methylation at C27 by the Evans method.     

Studies toward the total synthesis of tedanolide: stereoselective synthesis of the C(8)-C(17) segment

The stereoselective synthesis of the C(8)-C(17) sub-unit (−)-5 of tedanolide (1), which involves iterative Evans aldol reactions as the key steps, is described.     

Enantioselective synthesis of the C1-C6 and C7-C23 fragments of the proposed structure of iriomoteolide 1a

Synthesis of the C1-C6 and C7-C23 fragments of the proposed structure of iriomoteolide 1a has been accomplished. Key steps include a cross metathesis to form the C15-C16 E olefin and a chelation controlled Grignard addition to form the tertiary alcohol at C14. Notably, 7 of the 9 stereocenters of the proposed structure have been set using various aldol reactions employing metallo enolates of thiazolidinethiones.     

Stereocontrolled synthesis of the C8-C22 fragment of rhizopodin

A convergent synthesis of the central C8-C22 core of the potent macrolide antibiotic rhizopodin is reported. Notable features of the stereocontrolled approach include an asymmetric reverse prenylation of an alcohol using a method of Krische, a thiazolium catalyzed transformation of an epoxyaldehyde as described by Bode, and a late-stage oxazole formation from advanced intermediates. This route demonstrates the applicability of these methodologies in complex natural product synthesis.     

A catalytic enantioselective hetero Diels-Alder approach to the C20-C32 segment of the phorboxazoles

[reaction: see text] An efficient synthesis of the C20-C32 segment of the phorboxazoles has been achieved using an enantioselective hetero Diels-Alder reaction catalyzed by Jacobsen's Cr(III) amino indanol Schiff base catalyst.     

Enantioselective allyltitanation. Efficient synthesis of the C1-C14 polyol subunit of amphotericin B

[structure] An efficient synthesis of the C(1)-C(14) fragment of amphotericin B is described. This synthesis is based on the formation of syn-1,3-diols from enantioselective allyltitanation of unprotected beta-hydroxyaldehydes.     

Total synthesis of scytophycin C. 1. Stereoselective syntheses of the C(1)-C(18) segment and the C(19)-C(31) segment

[structure: see text] Stereoselective total synthesis of scytophycin C, a marine 22-membered macrolide displaying potent activity against a variety of human carcinoma cell lines, has been reported in which the polypropionate structure bearing contiguous asymmetric centers was stereospecifically constructed by using new acyclic stereocontrol. This paper describes stereoselective syntheses of the C(1)-C(18) segment (Segment A) including a trans-disubstituted dihydropyran ring and the C(19)-C(31) segment (Segment B) having eight stereogenic centers.     

Design and synthesis of C6-C8 bridged epothilone A

A conformationally restrained epothilone A analogue (3) with a short bridge between methyl groups at C6 and C8 was designed and synthesized. Preliminary biological evaluation indicates 3 to be only weakly active (IC50 = 8.5 microM) against the A2780 human ovarian cancer cell line.     

Amphidinolide B: asymmetric synthesis of a C7-C20 synthon

[reaction: see text] An asymmetric synthesis of a C(7)-C(20) synthon of amphidinolide B is described. The synthesis entails the construction of C(7)-C(13) and C(14)-C(20) fragments and makes extensive use of catalytic asymmetric bond constructions to establish the requisite stereochemical relationships. Fragment coupling proceeds by Suzuki cross-coupling and installs the trisubstituted diene unit that is among amphidinolide B's defining structural features.     

Synthetic studies of incednine: synthesis of C1-C13 pentaenoic acid segment

Stereoselective synthesis of the C1-C13 pentaenoic acid segment (4) of the novel antibiotic incednine (1) is described.