Studies on the synthesis of apoptolidin: synthesis of a C1-C27 fragment of apoptolidin D

Synthesis of a C(1)-C(27) fragment, a key intermediate in the synthesis of apoptolidin D, is reported. The synthesis involves a combination of Heck coupling and Horner-Wadsworth-Emmons reaction for the C(1)-C(7) trienoate portion and an efficient Suzuki cross-coupling protocol for the C(10)-C(13) diene portion.     

Enantioselective preparation of the C1-C11 fragment of apoptolidin

[reaction: see text] A novel approach toward the synthesis of the triene portion of the biologically active polyketide apoptolidin is described. The use of an iterative thionyl chloride rearrangement/oxidation sequence to construct trisubstituted olefins is explored.     

Synthesis of the C(1)-C(11) polyene fragment of apoptolidin with a new sulfur dioxide-based organic chemistry

A new sulfur dioxide-based organic chemistry has been developed as a novel approach for the stereoselective synthesis of polyene fragments based on our one-pot, four-component synthesis of polyfunctional epsilon-alkanesulfonyl-gamma,delta-unsaturated ketones. The flexibility and efficiency of this methodology are illustrated by the preparation of (+)-methyl (2E,4E,6E,8R,9S)-9-{[(tert-butyl)dimethylsilyl]oxy}-2,4,6,8-tetramethyl-11-(triethylsilyl)undeca-2,4,6-trien-10-ynoate, a synthetic intermediate of Nicolaou and co-workers, that corresponds to the C(1)-C(11) fragment of apoptolidin, which was used by the authors in their total synthesis of this promising anticancer agent.     

Stereoselective synthesis of the C(1)-C(11) fragment of peloruside A

A highly stereoselective synthesis of the C(1)-C(11) fragment 4 of peloruside A has been accomplished via a stereoselective double allylboration and an intramolecular epoxide opening to provide the functionally dense C(3)-C(11) segment 14. A glycolate aldol reaction was then employed to introduce the remaining stereocenters at C(2)-C(3). [reaction: see text]     

Synthesis of the apoptosis inducing agent apoptolidin. Assembly of the C(16)-C(28) fragment

[reaction--see text] A stereoselective synthesis of the C(16)-C(28) fragment of the apoptosis inducing agent apoptolidin is described. Key steps include two propionate aldol reactions and a stereoselective Mukaiyama aldol addition of enolsilane 19 to beta-methoxy aldehyde 4.     

Short synthesis of the C16-C28 polyketide fragment of apoptolidin A aglycone

Starting from (E,E)-1-[(1R)-(phenylethyl)oxy]-2-methylpenta-1,3-diene and triethylsilyl enol ether of butanone rapid access to Koert's advanced C10-C28 polyketide fragment of apoptolidin A is now possible.     

Studies on the synthesis of tedanolide. 2. Stereoselective synthesis of a protected C(1)-C(12) fragment

[reaction: see text] Highly diastereoselective syntheses of diketo esters 6a and 6b are described. These intermediates undergo efficient aldol reactions with protected C(13)-C(21) aldehydes 3 and 23, thereby providing advanced C(1)-C(21) tedanolide seco ester precursors 9a and 9b.     

Efficient synthesis of the C(1)-C(11) fragment of the tedanolides. The nonaldol aldol process in synthesis

[reaction: see text] The nonaldol aldol process developed in our laboratories has been applied to the synthesis of a C(1)-C(11) fragment 22 of the novel macrocyclic cytotoxic agents tedanolide and 13-deoxytedanolide 1 and 2. The commercially available hydroxy ester 7 was converted in 24 steps into compound 22 using two nonaldol aldol reactions.     

Synthesis of macrolide antibiotics. 16. Synthesis of erythronolides A and B by a coupling scheme of (C5-C9) + (C3-C4) + (C1-C2) + (C10) + (C11-C13) fragments and synthesis of the C5-C9 fragment

Conclusions A synthesis of a C⁵-C⁹-fragment common to erythronolides A and B was carried out starting from levoglucosan.For previous communications, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 674–680, March, 1989.     

Synthesis of southern (C1′-C11′) fragment of pamamycin-635A

The synthesis of the southern (C1′-C11′) fragment of pamamycin-635A, isolated from Streptomyces alboniger, was achieved via an Evans aldol reaction, a cis-selective iodoetherification and a stereospecific deiodination as the key steps.     

Studies on the total synthesis of sanglifehrin A: stereoselective synthesis of the C(29)-C(39) fragment

A highly stereoselective synthesis of the C(29)-C(39) fragment of the potent immunosuppressant sanglifehrin A has been accomplished by a sequence involving 16 steps (18% overall yield) from N-propionyloxazolidinone 9. Key steps are a diastereoselective hydroboration, and a diastereoselective epoxidation of an allylic alcohol followed by a 1,5-anti boron-mediated aldol reaction of methyl ketone 4 with chiral aldehyde 5.     

A stereoselective synthesis of the C(1)-C(16) fragment of the bryostatins

A synthesis of the C(1)-C(16) fragment of the brysostatins has been developed. Key steps are the stereoselective copper(I) catalysed addition of allylmagnesium bromide to an alkynyl ester, a condensation of a βγ-unsaturated aldehyde with a ketophosphonate, and the formation of the B-ring under mild conditions by stereoselective intramolecular conjugate addition.     

Stereoselective synthesis of the C(1)-C(19) fragment of tetrafibricin

[reaction: see text] A stereoselective synthesis of the C(1)-C(19) fragment of tetrafibricin has been accomplished via a highly diastereoselective double allylboration reaction of 6-8 and an iodonium ion promoted urethane cyclization for the installation of the C(15) alkoxy function in 3.     

Synthesis of C(1)-C(11) oxygen-bridged pregnanes

A general procedure for the synthesis of 1α,11α- and 1β,11α-epoxysteroids is described, using an intramolecular remote functionalization reaction involving the photolysis of 11α-hydroxysteroids in the presence of diacetoxyiodobenzene and iodine. Three 1,11-epoxypregnanes were prepared, two of them (compounds 10 and 14) are conformationally constrained analogues of steroidal hormones, compound 13 is a synthetic precursor of neurosteroids.     

Synthesis of a C(1)-C(14)-containing fragment of callipeltoside A

[formula: see text] A C(1)-C(14)-containing fragment of callipeltoside A (1, Scheme 1) was synthesized efficiently via a dianion aldol coupling reaction between aldehyde 2 and ketoester 3. A surprising lack of reactivity between the alkenes in 13 and the Grubbs initiator 15 was encountered. An equally surprising rate acceleration of the reaction between 15 and allylic alcohols (alk-1-en-3-ols) as well as their subsequent cleavage to methyl ketones was discovered. In situ 1H NMR analysis has proven to be a very useful tool for monitoring RCM reactions of complex substrates such as 13.     

Studies on the synthesis of apoptolidin A. 2. Synthesis of the disaccharide unit

Disaccharide 3 correspoinding to the disaccharide unit of apoptolidin A has been synthesized via the regio- and stereoselective TBS-OTf-promoted beta-glycosidation reaction of 2,6-dideoxy-2-iodo-beta-glucopyranosyl acetate (5) and p-methoxybenzyl 2,6-dideoxy-2-iodo-3-C-methyl-alpha-mannopyranoside (11).     

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.     

Enantioselective synthesis of the C1-C11 fragment of bafilomycin A1 using non-Wittig and desymmetrization strategies

The synthesis of the C1-C11 fragment 33 of bafilomycin A(1) was achieved. Intermediate ketone 16 was prepared in six steps from 4-oxopimelate 13. Desymmetrization of this ketone using Koga's chiral base followed by TMSCl quench furnished silyl enol ether 17 with excellent enantioselectivity. Further elaboration led to C5-C11 aldehyde 24, which was coupled with sulfone 3 to give lactone 25 in very good yield. The subsequent reductive elimination created the E-trisubstituted C4-C5 olefin with a 13:1 selectivity. The E C2-C3 double bond was then installed by methanol elimination, and compound 33 was obtained after a few functional group manipulations and a Negishi methyl zirconation.     

Synthesis of the C1-C13 fragment of leucascandrolide A

[reaction: see text] The synthesis of the C1-C13 fragment 3 of leucascandrolide A has been completed utilizing a stereoselective and regioselective reductive cleavage of a highly functionalized spiroketal to incorporate the cis-2,6-disubstituted tetrahydropyan. The spiroketal was constructed by addition of a lithiated pyrone 5 to aldehyde 6.     

Synthesis of the C1-C23 fragment of Spirastrellolide A

Synthesis of the C1-C23 fragment in spirastrellolide A is described, featuring a cyclic acetal-tethered RCM for stereoselective constructions of spiroketal, and a 1,3- anti aldol involving methyl ketone enolate and Mukaiyama conditions.