Stereoselective synthesis of C19–C27 fragment of bryostatin 11

A convergent synthesis of C19–C27 fragment (2) of bryostatin-11 is described. The key steps involved in this approach are kinetic resolution, Grignard reaction, and Sharpless dihydroxylation. AIBN catalyzed radical cyclization strategy has been used for the first time to construct the six-membered pyran system.     

An improved synthesis of the C42–C52 segment of ciguatoxin 3C

In our previously reported method for the construction of the IJKLM-ring of ciguatoxin 3C (CTX3C), the lengthy synthetic process for the intermediate C42–C52 (L-ring) segment was problematic. Therefore, a new and improved procedure for the C42–C52 segment, having modified protecting groups, was developed. The new route includes a chirality transferring Ireland-Claisen rearrangement for the construction of the vicinal dimethyl branching at C47–48, a one-pot cyclization process for the establishment of the stereocenters at C45 and C46 as well as the γ-hydroxy δ-lactone framework corresponding to the L-ring, and Brown’s asymmetric crotylboration for the installation of the stereocenters at C43 and C44. The new C42–C52 segment was successfully coupled with the previously reported C32–C41 (I-ring) segment to produce the IJKLM-ring.     

Total synthesis of (±)-cylindricine C

A concise synthesis of (±)-cylindricine C and its C(13)-epimer is described. Starting from 1-octyne, cylindricine C and 13-epi-cylindricine C were prepared in 11% and 15% yields, respectively. The synthesis involves the preparation of the central tricyclic moiety via a radical α-iodoketone carboazidation/bis-reductive amination sequence. Inversion of the stereochemistry at C(13) and C(5) was efficiently achieved on late stage intermediates.     

Stereoselective synthesis of C15C24 and C25C30 fragments of dolabelides

The stereocontrolled synthesis of a C15C24 fragment of dolabelides is reported. The C19 and C21 hydroxyl-bearing stereocenters were installed using ruthenium-mediated asymmetric hydrogenations of cyclic hemiketal 4 and β-keto ester 7. The C25C30 portion of dolabelides was prepared as well by ring opening of chiral epoxy alcohol 12 to set up the C27 stereogenic center.     

Toward the stereoselective synthesis of C1–C23 fragment of spirastrellolide B

A convergent synthesis of the protected C(1)–C(23) fragment 4 of the targeted natural product spirastrellolide B is described. The key step of the synthesis is cross metathesis (CM) and TBAF promoted oxa-Michael to construct tetrahydropyran moiety.     

Stereo selective synthesis of C3–C12 fragment of iriomoteolide-1a

A convergent and flexible synthetic route for the synthesis of C3–C12 fragment of iriomoteolide-1a is described. The key steps are: Mannich reaction, Keck asymmetric allylation, Sharpless asymmetric epoxidation and cross-metathesis protocol.     

Stereoselective synthesis of C12–C21 common fragment of thermolides 1–5

A highly stereoselective synthesis of C12–C21 common fragment of thermolides 1–5 has been described. The salient features of the synthesis are the utilization of desymmetrization protocol, Barton-McCombie reaction, Brown’s asymmetric allylation and Wacker oxidation.     

Gram scale synthesis of the C(1)–C(9) fragment of amphidinolide C

An allylic cis-epoxide prepared by Sharpless asymmetric epoxidation was transformed in nine steps and 41% overall yield to the cyclization precursor 4 via a key one carbon homologation. Cobalt-catalyzed aerobic oxidative cyclization of 4 gave the trans-THF in 94% yield at gram scale. Subsequent manipulations, including a Still–Gennari olefination, Sharpless asymmetric dihydroxylation, Corey–Fuchs alkynylation, and Kazmaier hydrostannylation provided the fully functionalized C(1)–C(9) fragment 2 suitable for cross-coupling. The sequence is readily scalable and provides gram quantities of 2.     

Total synthesis of (±)-pallambins C and D

The first total synthesis of (±)-pallambins C and D has been accomplished in a linear 38 step reaction from (±)-Wieland-Miescher ketone. The key conversions are featured as follows: a Grob fragmentation-intramolecular aldol cyclization and a thiourea/palladium-catalyzed carbonylative annulation.     

Fast and protecting-group-free synthesis of (±)-subincanadine C

The first total synthesis of (±)-subincanadine C has been accomplished in a protecting-group-free fashion. This pentacyclic indole alkaloid was synthesized in six steps from the known intermediate 4, featuring Ni(COD)(2)-mediated intramolecular Michael addition as a key transformation.     

Stereoselective synthesis of C3–C17 and C18–C34 subunits of bullatanocin utilizing α-chloro sulfide intermediates

A convergent synthesis of bullatanocin is envisaged by the union of C18–C34, C3–C17 and the butenolide subunits. The synthesis of the C3–C17 and C18–C34 subunits is disclosed that takes advantage of the chirality of tartaric acid for 1,2-asymmetric induction, chloro sulfides for carbon chain elongation and [2,3] sigmatropic shift for the preparation of 1,4-diol moiety via efficient 1,3-chirality transfer. The THF ring is elaborated by intramolecular displacement.     

Enantioselective synthesis of allenecarboxylates from phenyl acetates through CC bond forming reactions

A variety of optically active 4,4-disubstituted allenecarboxylic acid methyl esters were prepared from simple α,α-disubstituted phenyl acetate through base treatment of the esters to generate ketenes, followed by successive Horner–Wadsworth–Emmons reaction. The transformation was further developed as a one-pot procedure with satisfactory yields and high enantioselectivity.     

Electrochemical and photochemical approaches for the synthesis of the C28–C38 fragment of okadaic acid

Okadaic acid, a potent and selective inhibitor of Protein Phosphatases 1 and 2A (PP1 and PP2A), is widely used as a probe for various biochemical processes. We describe herein two innovative methods for the synthesis of the terminal C28–C38 fragment of the natural polyether. Suárez photochemical oxidative cyclization and electrochemical oxidation of malonates to their ketals equivalents have been successfully applied for the assembly of the key spiroketal core.     

Asymmetric synthesis of the C1–C6 portion of the psymberin using an Evans chiral auxiliary

The C1–C6 region of the potent cytotoxic agent psymberin has been synthesized. The key transformations of the synthesis are an auxiliary-controlled addition of a Sn(II)-glycolate enolate to an aldehyde to yield the anti-aldol product and transforming the primary alcohol into a terminal olefin utilizing organoselenium chemistry.     

Visible light promoted synthesis of N-aroylsulfoximines by oxidative C–H acylation of NH-sulfoximines

The visible light-promoted synthesis of N-aroylsulfoximines has been accomplished via an oxidative dehydrogenative coupling at room temperature under air without the addition of a photosensitizer, metal catalyst, or base. This process exhibits good functional group tolerance, allows facile isolation and purification, and affords N-aroylsulfoximines with high efficiency. The efficiency of the newly developed protocol is described in detail with 27 examples with yields ranging from 80% to 96%.Furthermore, the chirality of the NH-sulfoximine is completely maintained in the desired N-aroylsulfoximine product(99% ee).     

Enantioselective synthesis of herbertane sesquiterpenes: synthesis of (−)-α-formylherbertenol

The synthesis of 4-hydroxy-3-[(1S)-1,2,2-trimethylcyclopentyl]benzaldehyde [(−)-α-formylherbertenol 1], a herbertane-type sesquiterpene isolated from the leafy liverwort Herberta adunca, from β-cyclogeraniol is described. The synthesis is based on the previously described preparation of an enantiopure 1,2,2-trimethylcyclopentane synthon from which the characteristic aromatic moiety of 1 is elaborated, using a Robinson annulation and a palladium-catalysed methoxycarbonylation of an aryl triflate as key synthetic steps. The synthesis of the natural sesquiterpene (−)-α-herbertenol, also a natural sequiterpene, using the same methodology is also described.     

Enantioselective synthesis of C2-symmetric hexols from β,δ-diketosulfoxides

An enantioselective synthesis of (1,2S,4S,8S,10S,11)-hexahydroxyundecane, a C₂-symmetric hexol precursor of the alkaloid (−)-lythranidine, is described. This convergent synthesis was based on the stereoselective reduction of two different β,δ-diketosulfoxides.     

Total synthesis of (±)-trigonoliimine C via oxidative rearrangement of an unsymmetrical bis-tryptamine

We report the first total synthesis of (±)-trigonoliimine C, a member of a family of structurally complex alkaloids, in 10 steps from tryptamine and 6-methoxytryptamine. Our convergent synthetic strategy relies on a selective oxidative rearrangement of an unsymmetrical 2,2'-bis-tryptamine.