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 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 total synthesis of nemorosone

The highly stereoselective total synthesis of nemorosone via a new approach to the bicyclo[3.3.1]nonane-2,4,9-trione core which features intramolecular cyclopropanation of an α-diazo ketone, stereoselective alkylation at the C8 position, and regioselective ring-opening of cyclopropane is described. The total synthesis of nemorosone includes chemo- and stereoselective hydrogenation directed by the internal alkene.     

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.     

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.     

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]     

The first stereoselective and the total synthesis of Leiocarpin C and total synthesis of (+)-Goniodiol

The synthesis of the styryl lactone Leiocarpin C has been achieved in a highly stereoselective manner using Jacobsen’s kinetic resolution, Sharpless asymmetric epoxidation and Sharpless asymmetric dihydroxylation as key steps. This is the first total synthesis of Leiocarpin C, and thus establishes for the first time the absolute stereochemistry of this natural product.     

Studies directed towards the synthesis of botcinolides: synthesis of the nonalactone ring of 2-epibotcinolide

Synthesis of the polyoxygenated nonalactone ring of 2-epibotcinolide was achieved using a highly stereoselective aldol reaction of the titanium enolate from a lactate-derived chiral ketone, a stereoselective dihydroxylation and a Yamaguchi macrolactonization reaction.     

Studies directed towards the total synthesis of botcinic acid, the revised structure of botcinolide: synthesis of the highly substituted tetrahydropyran moiety

Synthesis of the highly substituted polyoxygenated tetrahydropyran ring of botcinic acid, the revised structure of botcinolide is achieved using, as key steps, a highly stereoselective aldol reaction of the titanium enolate from a lactate-derived chiral ketone and a stereoselective dihydroxylation.     

Stereoselective synthesis of the western hemisphere of salinomycin

[structure: see text]. A convergent and module-based strategy for the asymmetric synthesis of the western hemisphere (C1-C17 fragment) of salinomycin has been devised. This new synthetic approach relies on highly stereoselective C-glycosidation and aldol processes.     

An efficient asymmetric synthesis of manzacidin C

A brief synthesis of manzacidin C based on a chiral silane-promoted diastereo- and enatioselective acylhydrazone-alkene [3 + 2] cycloaddition reaction has been achieved. This synthesis is the first synthesis of any of the manzacidins wherein the C(4) and C(6) stereocenters are established in a single highly stereoselective step.     

Total synthesis of gymnocin-A

A highly convergent total synthesis of gymnocin-A, a cyctotoxic polyether marine natural product, has been achieved. The synthesis features Suzuki-Miyaura coupling of the ABCD and FGHIJKLMN rings, stereoselective introduction of the C17 hydroxyl group, ring-closure of the F ring, and a late-stage incorporation of a 2-methyl-2-butenal side chain.     

The first total synthesis of concanamycin f (concanolide a)

A highly stereoselective total synthesis of the macrolide antibiotic concanamycin F (1), a specific and potent inhibitor of vacuolar H(+)-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 18-membered tetraenic lactone and beta-hydroxyl hemiacetal side chain subunits. The C1-C19 18-membered lactone aldehyde 4 was synthesized through the intermolecular Stille coupling of the C5-C13 vinyl iodide 24 and the C14-C19 vinyl stannane 25, followed by construction of the C1-C4 diene and macrolactonization. Synthesis of 4 via a second convergent route including the esterification of the C1-C13 vinyl iodide 45 and the C14-C19 vinyl stannane 47 followed by the intramolecular Stille coupling was also realized. The highly stereoselective aldol coupling of 4 and the C20-C28 ethyl ketone 5 followed by desilylation provided 1 which was identical with natural concanamycin F.     

Total synthesis of (+)-lepadin F

An enantioselective total synthesis of (+)-lepadin F is described. The synthetic sequence features an intermolecular aza-[3 + 3] annulation, homologation of a vinylogous amide via Eschenmoser's episulfide contraction, and a highly stereoselective hydrogenation essential for achieving the 1,3-anti relative stereochemistry at C2 and C8a.     

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.     

Progress toward the total synthesis of bafilomycin A(1): stereoselective synthesis of the C15-C25 subunit by additions of nonracemic allenylzinc reagents to aldehydes

[reaction: see text] A highly stereoselective synthesis of the C15-C25 subunit (2) of bafilomycin A(1) (1) has been accomplished by a route utilizing additions of chiral nonracemic allenylzinc reagents to aldehydes.     

Total synthesis of (+)-tedanolide

A convergent, stereocontrolled total synthesis of (+)-tedanolide (1), an architecturally complex marine antitumor macrolide, has been achieved in 31 steps (longest linear sequence). Highlights of the synthesis comprise a highly efficient dithiane union, followed by an Evans-Tishchenko "oxidation" to enable formation of the seco-ester in the presence of an oxidatively labile dithiane, a highly refined protecting group strategy, and a chemo- and stereoselective epoxidation at C(18,19).     

Total synthesis of ingenol

Total synthesis of ingenol, a diterpene isolated from the genus Euphorbia, was accomplished on the basis of the novel key reactions. The highly strained ingenane skeleton was constructed through an intramolecular cyclization reaction of an acetylene dicobalt complex followed by a rearrangement reaction of an epoxy alcohol. The C(3),C(4),C(5)-triol moiety was introduced by a stereoselective double dihydroxylation reaction of a diene having C(2)-C(3) and C(4)-C(5) double bonds.     

Large-scale synthesis of SB-462795, a cathepsin K inhibitor: the RCM-based approaches

Two stereoselective syntheses of SB-462795, a highly potent cathepsin K inhibitor, are described. Both routes feature a C5-C6 disconnection by ring closing metathesis to construct an azepane ring and are amenable to large-scale manufacturing.