Double intramolecular oxymercuration: stereoselective synthesis of highly substituted bis-tetrahydrofuran

Stereoselective intramolecular oxymercuration has been demonstrated as the key reaction for the efficient preparation of mono- and dihydroxylated unsymmetrical bis-tetrahydrofuran skeletons present in naturally occurring biologically active acetogenins using carbohydrates. These trans- and syn-selective intramolecular oxymercurations were explored in an enantioselective synthesis of the bis-tetrahydrofuran skeleton of mucoxin.     

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.     

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.     

A stereoselective total synthesis of (±)-tormesol

A general strategy for the synthesis of both trans/syn- and trans/anti-sphenolobane diterpenes has been developed, which utilizes an intramolecular ester enolate alkylation (IEEA) as a key step. A stereoselective total synthesis of (±)-tormesol (1), an unusual trans/syn-sphenolobane diterpene, was accomplished in 18 steps in 4.1% overall yield from readily available aldehyde 16.     

Studies towards the total synthesis of narbonolide: stereoselective preparation of the C1-C10 fragment

An efficient stereoselective synthesis of the C1-C10 fragment of narbonolide is reported. The stereocentres at C2, 3, 4, 5, 8 and 9 in fragment 5 can be generated via an iterative asymmetric acyl-thiazolidinethione aldol reaction, whereas the stereocentre at C6 is installed by means of Myers alkylation.     

Stereoselective synthesis of the C1-C13 fragment of bistramide A

The C1-C13 fragment of bistramide A was prepared from 5-hexenoic acid in 15 linear steps and in 16% overall yield. The core 2,6-trans-tetrahydropyran ring was obtained via a kinetically controlled oxa-Michael cyclization from the corresponding chiral α,β-unsaturated hydroxyester. This precursor was prepared by using a diastereoselective alkylation reaction using Davies Superquat auxiliary and a diastereoselective Roush’s allylboration as key steps.     

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.     

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.     

A highly stereoselective synthesis of the C10-C23 fragment of (-)-dictyostatin

A highly stereoselective synthesis of the C10-C23 fragment of (-)-dictyostatin has been achieved using a Carreira alkynylation and a Marshall-Tamaru allenylzinc addition 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.     

Total synthesis of (+)-cylindricine C

A stereoselective total synthesis of (+)-cylindricine C has been achieved starting with (S)-N-Boc-2-pyrrolidinone. The key elements of this synthesis involve the sequence of reactions including BF₃-mediated addition of the allyl Grignard reagent to the cyclic imine, spirocyclization via enamine formation, and intramolecular Michael addition to form the tricyclic core.     

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.     

The stereoselective total synthesis of xestodecalactone C and epi-sporostatin via the Prins cyclisation

Syntheses of xestodecalactone C and epi-sporostatin are described utilising Prins cyclisations, Mitsunobu reaction and intramolecular Friedel-Crafts acylation. The approach is convergent and highly stereoselective.     

A stereoselective synthesis of the C11-C19 fragment of (+)-peloruside A

A new route to the synthesis of the C11-C19 fragment of peloruside A is described, which includes an aldol reaction with ethyl acetoacetate, β-hydroxyl-directed reduction of β-hydroxy ketone, as well as methylation of C13 hydroxyl moiety in the system of MeI-Ag₂O-MgSO₄-CH₂Cl₂.     

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.     

Stereoselective synthesis of the C1-C10 fragment of rhizoxin D

A novel approach towards the synthesis of the C1-C10 fragment of the biologically active antimitotic agent rhizoxin D is described. The synthesis involves a stereoselective Michael addition reaction of lithium diallyl cuprate with an α,β-unsaturated six membered lactone.     

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.     

Towards the total synthesis of amphidinolide E: an enantioselective synthesis of C12-C29 fragment

An enantioselective synthesis of the C12-C29 fragment of amphidinolide E is described. Key transformations include an intramolecular mercuriocyclization reaction, stereoselective introduction of methyl group at the C2 position, and Stille coupling for the introduction of the diene side chain.     

Iterative deoxypropionate synthesis based on a copper-mediated directed allylic substitution: formal total synthesis of borrelidin (C3-C11 fragment)

A new iterative strategy for the flexible preparation of any oligodeoxypropionate stereoisomer is presented which relies on an o-DPPB-directed copper mediated allylic substitution employing enantiomerically pure Grignard reagents; the reaction is working with perfect control over all aspects of the reaction selectivity. This key C--C bond-forming step features reversed polarity compared with established enolate alkylation methodology. It thus avoids existing problems of enolate alkylation strategies such as enolate reactivity as well as costs and problems associated with the chiral auxiliary. Practicability of this new method is demonstrated through application in natural product syntheses. Thus, an efficient synthesis of the northern part of the angiogenesis inhibitor borrelidin (28), the deoxypropionate building block 27, could be devised, representing a formal total synthesis.     

A facile approach to the synthesis of securinega alkaloids: stereoselective total synthesis of (−)-allonorsecurinine

A concise stereoselective total synthesis of alkaloid (−)-allonorsecurinine is described utilizing classical reactions such as Grignard, Aldol and Horner-Wittig reactions as the key steps.