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.     

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 directed toward the total synthesis of discodermolide: asymmetric synthesis of the C1-C14 fragment

[structure: see text] A convergent and stereoselective assembly of the C1-C14 subunit of marine natural product (+)-discodermolide has been completed. The approach employs chiral allylsilane bond construction methodology to establish four of the eight stereogenic centers. Key fragment coupling is achieved via an efficient stereoselective acetate aldol reaction between C1-C6 and C7-C14 subunits.     

Highly stereoselective synthesis of methynolide,the aglycone of the 12-membered ring macrolide methymycin,from D-glucose

A highly stereoselective and efficient synthesis of methynolide, the aglycone of 12-membered macrolide methymycin, was achieved from of C1–C8 and C9–C13 segments synthesized from D-glucose by employing some stereoselective reactions and benzyl-type protecting groups.     

Studies directed toward the total synthesis of pinnatoxin A: synthesis of the 6,5,6-dispiroketal (BCD ring) system by double hemiketal formation/hetero-Michael addition strategy

An efficient, highly stereoselective synthesis of the C10–C26 portion of pinnatoxin A has been achieved, wherein the key step is a highly stereoselective construction of the 6,5,6-dispiroketal (BCD ring) system by an intramolecular hetero-Michael addition of a hemiketal alkoxide reversibly formed under the influence of lithium methoxide.     

Stereoselective synthesis of C-substituted morpholine derivatives using reductive etherification reaction: total synthesis of chelonin C

A general strategy is developed for the stereoselective synthesis of C-substituted morpholine derivatives using intramolecular reductive etherification reaction. The method is extended to the first stereoselective total synthesis of (±)-chelonin C.     

Stereoselective synthesis of both tetrahydropyran rings of the antitumor macrolide, (-)-lasonolide A

Stereoselective syntheses of both functionalized tetrahydropyran subunits of (-)-lasonolide A are described. These tetrahydropyran rings were constructed using catalytic asymmetric hetero Diels-Alder reactions as the key steps. The C22 quaternary stereocenter present in the upper tetrahydropyran ring was constructed by a stereoselective alkylation, and the C9 hydroxy stereochemistry of the bottom tetrahydropyran was constructed by a stereoselective epoxidation followed by a regioselective epoxide opening reaction.     

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]     

P-heterocyclic building blocks: application to the stereoselective synthesis of P-sugars

A strategy relying on the utilization of stereoselective additions to allyldiphenylphosphonate esters and subsequent ring-closing metathesis (RCM) to access P-chiral P-heterocyclic building blocks for the synthesis of phosphono sugars is described. These building blocks possess several attractive components, including the following: (i) P(2) and C(6) stereogenic centers for directing stereoselective transformations; (ii) an activated C(3) methylene group that promotes base-mediated olefin transposition to generate vinyl phosphonates available for further stereoselective reactions; and (iii) a P(2)-stereogenic center containing an exchangeable phosphonate ester armed to attenuate the "stereochemical environment" at phosphorus. Taken collectively, these attributes contribute to a concise method for the stereoselective synthesis of an array of P-sugars.     

Stereoselective synthesis of the C21C27 fragment of the phorboxazoles

A stereoselective synthesis of the C21C27 fragment of phorboxazoles A and B was achieved in 12 linear steps via an intramolecular cyclization induced by mercury acetate, to afford a functionalized tetrahydropyran.     

Studies directed toward the synthesis of the massileunicellins

An approach to the massileunicellins is described that employs a cycloaldol reaction to assemble the isobenzofuran bicyclic core. A stereoselective rearrangement-epoxidation-oxidation cascade and a chelation controlled addition to a hindered acyl furan are used to install the C3, C11, C12, and C13 oxygens. The synthesis establishes eight of the nine stereocenters present in the isobenzofuran core of the massileunicellins.     

Modular synthesis of the C9-C27 degradation product of aflastatin A via alkyne-epoxide cross-couplings

A modular approach to the synthesis of complex polyketide natural products is demonstrated for the synthesis of the C9-C27 degradation product from aflastatin A. The product of the cross-coupling of C23-C27 terminal alkyne with C17-C22 epoxide underwent functionalization of the resulting internal alkyne, which was then coupled similarly with C9-C16 epoxide. This synthesis concluded with regio- and stereoselective addition of methyl onto the internal alkyne followed by stereoselective hydroboration-oxidation.     

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.     

A stereoselective synthesis of (+)-herboxidiene/GEX1A

A stereoselective synthesis of (+)-herboxidiene is described. The convergent synthesis utilized a Suzuki cross-coupling reaction to assemble the key segments. The synthesis of the functionalized tetrahydropyran ring utilized an Achmatowicz reaction as the key step. The synthesis of the C10-C19 segment was accomplished using Brown's crotylboration, asymmetric alkylation, and a stereoselective allylic chlorination reactions.     

Stereoselective synthesis of methyl 7-dihydro-trioxacarcinoside B

A stereoselective synthesis of 7-dihydro-triocacarcinose B, a branched octose from the quinocyclines, has been achieved. The biocatalytic resolution of a Baylis-Hillman adduct and a subsequent ring-closing metathesis were used to assemble the molecular framework. Subsequent key steps were a highly stereoselective epoxidation and a regio- and stereoselective opening of the epoxide by allyl alcohol and HClO4 to introduce the C(3)-OH group in protected form. The 7-dihydro-triocacarcinose B could be converted into the corresponding 1,7-anhydrosugar.     

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.     

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.     

Total synthesis of everninomicin 13,384-1--Part 3: synthesis of the DE fragment and completion of the total synthesis

The stereoselective construction of the DE fragment (2) of everninomicin 13,384-1 (1) is reported. From the two possible ways of inserting the DE fragment between the A1B(A)C and FGHA2 domains of the natural product, the sequence involving the DEFGHA2 segment was found to be the most viable. This coupling was followed by attachment of a suitably protected and activated A1B(A)C fragment which led, after orthoester construction and final deprotection to the targeted everninomicin 13,384-1 (1), completing the total synthesis of this complex naturally occurring substance.     

Stereoselective synthesis of the C33-C44 fragment of palau’amide

An efficient stereoselective synthesis of the C33-C44 fragment of palau’amide is described using a Sharpless asymmetric epoxidation, a regioselective nucleophilic ring opening of the epoxide, a Grignard reaction and a Luche stereoselective reduction of a keto compound as the key steps.     

Studies toward the total synthesis of gambieric acids, potent antifungal polycyclic ethers: convergent synthesis of the CDEFG-ring system

[reaction: see text] A convergent synthetic route to the CDEFG-ring system of gambieric acids, potent antifungal polycyclic ether marine natural products, has been developed. The present synthesis features convergent union of the CD- and G-rings through esterification, formation of the E-ring as a lactone form, stereoselective allylation to set the C26 stereocenter, and ring-closing metathesis reaction to construct the nine-membered F-ring.