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Our efforts toward the synthesis of the marine natural product portimine are described. The key to the synthesis of the skeleton is a stereoretentive copper-catalyzed C( sp 3 )-C( sp 2 ) Stille-type cross-coupling that enables the convergent assembly of functionalized fragments. The core skeleton of portimine was constructed via ring-closing metathesis and transannular acetal formation.

The total synthesis of marine macrolide glycoside (-)-irijimaside A is described. Key to the synthesis is the convergent fragment assembly enabled by nickel/zirconocene-mediated one-pot reductive ketone coupling. At the last stage of the synthesis, Stille coupling and glycosylation led to the first total synthesis of (-)-irijimaside A.

Synthesis of four diastereomers of the C1-C12 fragment of amphirionin-5 has been achieved in a convergent and stereodivergent manner. Detailed comparison of the (1)H and (13)C NMR data of each compound with those reported for the natural product led to not only the stereochemical assignment of the relative configuration of the C4/C5 stereogenic centers but also reassignment of the proposed relative configuration at C9 of amphirionin-5.

A convergent synthesis of the C1-C16 segment of goniodomin A, an actin-targeting marine polyether macrolide natural product, has been achieved via a 2-fold application of palladium-catalyzed organostannane-thioester coupling.

Total synthesis of (-)-exiguolide, the natural enantiomer, has been accomplished for the first time. The bis(tetrahydropyran) subunit was efficiently synthesized via consecutive olefin cross-metathesis/intramolecular oxa-conjugate addition/reductive etherification. Construction of the 20-membered macrocycle was achieved by Yamaguchi macrolactonization. Stereoselective introduction of the (E,Z,E)-triene side chain via Suzuki-Miyaura coupling completed the total synthesis.

Stereoselective convergent synthesis of the C15-C36 segment of goniodomin A, an actin-targeting marine polyether macrolide natural product, has been achieved. The present synthesis features palladium(0)-catalyzed, copper(I)-mediated Liebeskind-Srogl cross-coupling as the fragment assembly process.

Total synthesis of (-)-brevenal, a novel marine polycyclic ether natural product, is described. Highly efficient and scalable entries to the AB-ring exo-olefin and the DE-ring enol phosphate and a rapid construction of the C-ring by means of our Suzuki-Miyaura coupling-based strategy realized a concise synthesis of the pentacyclic skeleton of (-)-brevenal. The present synthesis is considerably more efficient than our previous synthesis (longest linear sequence: 50 steps from 2-deoxy-d-ribose).

Strategies have been developed for the synthesis of 2-substituted indoles and indolines starting from acyclic alpha-phosphoryloxy enecarbamates. A highly chemoselective cross-coupling of N-(o-bromophenyl)-alpha-phosphoryloxyenecarbamates with boron nucleophiles enabled the efficient preparation of various N-(o-bromophenyl)enecarbamates, which served as useful precursors for subsequent Heck-type cyclization or 5-endo-trig aryl radical cyclization to furnish 2-substituted indoles or indolines, respectively.

[structure: see text] An efficient and highly convergent synthesis of the FGHIJKLMN ring fragment of gymnocin A, a cyctotoxic polycyclic ether isolated from the notorious red-tide forming dinoflagellate Gymnodinium mikimotoi, has been achieved. The present synthesis relied on extensive use of the B-alkyl Suzuki-Miyaura coupling reaction.