Synthetic studies toward potent cytostatic macrolide rhizopodin: stereoselective synthesis of the C16-C28 fragment

A stereoselective synthesis of the C16-C28 fragment of cytostatic C₂-symmetric macrolide rhizopodin is described. Enantioselective addition of a chiral thiazolidinethione derived titanium enolate to acetal, Evans’ aldol reaction, Horner-Wadsworth-Emmons reaction, and Mukaiyama aldol reaction were applied as key steps.     

Synthetic studies on apoptolidin: synthesis of the C12-C28 fragment via a highly stereoselective aldol reaction

The stereoselective and convergent synthesis of the C12-C28 segment 2 of the apoptosis inducing macrolide antibiotic, apoptolidin (1), is described. The synthesis involves a highly stereoselective tin(II)-mediated aldol reaction between the C17-C22 ethyl ketone 3 and the C23-C28 aldehyde 4 as the key step.     

Studies directed toward the synthesis of rhizopodin: stereoselective synthesis of the C1-C15 fragment

A stereoselective synthesis of the C1-C15 fragment of a G-actin binding natural macrodiolide, rhizopodin was achieved using, as key steps, highly stereoselective acetate aldol reactions to build the C1-C7 fragment, one pot oxazole synthesis and an asymmetric Keck allylation reaction to build the C8-C15 fragment and finally, a Stille reaction to couple both the fragments.     

Studies toward the total synthesis of irumamycin: stereoselective preparation of the C(15)-C(27) segment via two-directional chain synthesis

The basic structure of the C(15)-C(27) part of irumamycin (1) was synthesized. Stereoselective assembly of C16, 17, 22, and an extra C21 stereocenter was achieved by two-directional Brown’s asymmetric allyl boration. Group selective PMP acetal formation and oxidative cleavage of vinyl group facilitated the differentiation of the ends of a two-directionally synthesized chain.     

Synthesis of C15-C27 segment of venturicidine X by utilizing desymmetrization protocol

We have achieved the synthesis of C15-C27 fragment of venturicidine X using desymmetrization protocol, substrate-controlled Grignard reaction, Barton-McCombie reaction, Sharpless epoxidation, and TBSOTf-mediated rearrangement to produce the aldol product through a non-aldol route as the key step following 23 longest linear sequences with 6.4% overall yield starting from a known intermediate 11.     

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.     

Synthetic studies on amphidinolides C and F: synthesis of the C18-C29 segment of amphidinolide F

The C18-C29 segment of amphidinolide F is synthesised in 12 steps from 1,4-butanediol. Key steps include a mono-Sharpless dihydroxylation of a dienoate, iodocyclisation to construct the trans-THF ring and an E-selective Wittig reaction to introduce the C25-C26 olefin.     

Synthetic studies on goniodomin A: convergent assembly of the C15-C36 segment via palladium-catalyzed organostannane-thioester coupling

A stereocontrolled convergent synthesis of the C15-C36 segment of goniodomin A, a potent anti-angiogenic marine polyether macrolide, has been achieved using Stille-type cross-coupling reaction of a vinylstannane and a thioester as a key segment assembly process.     

Synthetic studies on chartelline C: stereoselective construction of the core skeleton

What a core-ker! The title synthesis was achieved using a route featuring an intramolecular Mitsunobu reaction of a nosyl amide, stereoselective construction of the β-lactam, and formation of an enamide moiety by selenoxide elimination. The stereochemistry of the alkylation for the formation of the β-lactam was controlled by a secondary hydroxy group on the ten-membered ring. SEM=2-(trimethylsilyl)ethoxymethyl; TBS=tert-butyldimethylsilyl.     

Studies on the synthesis of phorboxazole B: stereoselective synthesis of the C28-C46 segment

A stereoselective synthesis of C28-C46 segment of phorboxazole B is described. Key features of the synthetic route involved the use of 1,3-asymmetric induction of Mukaiyama aldol reaction to construct the stereogenic center at C35, and the employment of metalated oxazole chemistry to prepare the ketal 6.     

Tetrafibricin: synthesis of the C1-C13, C15-C25, and C27-C40 fragments

[structure: see text] A sequence of chemoselective cross-metathesis reactions and enantioselective allyltitanations of aldehydes has been used to prepare the C1-C13, C15-C26, and C27-C40 fragments of tetrafibricin.     

Synthetic studies on borrelidin: enantioselective synthesis of the C1-C12 fragment

[structure: see text] An efficient, enantioselective synthesis of the C1-C12 fragment 2 of borrelidin is presented. Construction of the "skipped" polymethylene chain of 2 was accomplished by iteration of Myers' alkylation, while formation of the C3 stereocenter was achieved by Roush's asymmetric allylboration methodology.     

Studies directed towards the total synthesis of lycoperdinosides: stereoselective construction of the C1-C9 and C10-C21 segments of the molecules

The three chiral centres of the C1-C9 moiety of the six-membered lactone glycosides, lycoperdinosides A and B, have been derived from a common starting material containing a single chiral centre. In contrast, the C10-C21 segment of these molecules has been synthesized using, as key steps, a highly stereoselective aldol reaction, a Ti(III)-mediated opening of a trisubstituted epoxy alcohol and an efficient directed hydrostannylation of a suitably substituted internal alkyne.     

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.     

A cross-metathesis approach for the synthesis of tedanolide and 13-deoxytedanolide: stereoselective synthesis of the C3-C16 segment

A unified synthetic strategy has been devised for the synthesis of both tedanolide and 13-deoxytedanolide, which involves a cross-metathesis reaction as the key step. We report herein the stereoselective synthesis of the C3-C16 segment (+)-5b and subsequent manipulation of the C12-C13 double bond leading to the preparation of both tedanolides.     

Double intramolecular oxymercuration: the first stereoselective synthesis of the C10-C34 fragment of asimitrin

The first stereoselective synthesis of the C10-C34 fragment of asimitrin, a nonclassical acetogenin, has been achieved. A key feature of our approach is the application of stereoselective double intramolecular oxymercuration for the efficient preparation of a mono-hydroxylated unsymmetrical bis-THF ring with two flanking hydroxyl groups. A chelation-controlled Grignard reaction plays a pivotal role in the elaboration of a commercially available carbohydrate.     

Studies directed towards the synthesis of antascomicin A: stereoselective synthesis of the C22-C34 fragment of the molecule

A stereoselective synthesis of the C22-C34 fragment of the non-immunosuppressive immunophilin-binding natural product, antascomicin A was achieved using d-quinic acid as the starting material and highly stereoselective aldol reactions were employed, as key steps, to build the remaining stereocentres at C23, C26 and C27.     

Stereoselective synthesis of the C3-C15 fragment of callyspongiolide

The synthesis of C3-C15 fragment of callyspongiolide, a 14-membered macrolides isolated from the marine sponge Callyspongia sp., which was collected from the Indonesia, is reported. Highlights of the synthesis include construction of E-olefin through Julia-Kocienski olefination, Brown asymmetric allylation and base-induced elimination reactions for propargyl alcohol synthesis.     

Studies directed towards the synthesis of antascomicin A: stereoselective synthesis of the C1-C21 fragment of the molecule

A stereoselective synthesis of the C1-C21 fragment of the non-immunosuppressive immunophilin-binding natural product, antascomicin A was achieved using, as key steps, highly stereoselective Aldol reactions to build the C1-C17 fragment and a Nozaki-Hiyama-Kishi reaction to couple it with the remaining C18-C21 moiety.     

Synthetic studies toward phorboxazole A. stereoselective synthesis of the C(28)-C(46) side chain fragment

A stereoselective synthesis of the C(28)-C(46) fragment (3) of phorboxazole A is described. Key advances include an enantioselective allylation to establish the stereochemistry of the tetrahydropyran unit and a useful SmI(2)-mediated modification of the Barbier reaction of iodomethyloxazole 15 with aldehyde 14.