A convergent enantioselective total synthesis of cotylenin A is described. The A-ring fragment, prepared via the catalytic asymmetric intramolecular cyclopropanation developed in our laboratory, and the C-ring fragment, prepared from a known chiral compound via a modified acyl radical cyclization, were successfully assembled by the Utimoto coupling reaction. The formidable carbocyclic eight-membered ring of cotylenin A was efficiently constructed by a palladium-mediated cyclization. All the hydroxy groups in the scaffold were stereoselectively introduced, and a modified reducing reagent, Me 4 NBH(O 2 C i Pr) 3 , has been developed. The sugar moiety fragment was prepared via three consecutive carbon−oxygen bond-forming reactions, and the glycosylation was accomplished using Wan's protocol.C otylenin A (Figure 1) was initially isolated as a plant growth regulator; 1 however, biological studies later revealed that it induces the differentiation of murine and human myeloid leukemia cells and the apoptosis of a wide range of human cancer cell lines by combined treatment with interferon-α. 2 The crystal structure of cotylenin A in a complex with 14-3-3 protein and a phosphopeptide of H + -ATPase (QSYpTV-COOH) has been reported 3 to confirm that cotylenin A binds to inhibitory 14-3-3 interaction sites of C-RAF, pSer233, and pSer259 but not the activating interaction site, pSer621. Moreover, the combined treatment of cotylenin A with an anti-epidermal growth factor receptor antibody is reported to synergistically suppress tumor growth in vitro and in vivo, which provides a novel pharmacologic strategy for treatment of RAS mutant cancers. 4

Enantioselective formal total synthesis of damsin, which was isolated from Compositae Ambrosia maritima L., is described. The highly enantio- and diastereoselective catalytic Mukaiyama-Michael reaction and subsequent highly stereoselective epimerization shorten the synthetic steps. It is also reported that the enolate, which was formed by the reaction of β-keto sulfone with lithium naphthaenide, reacted with methyl cyanoformate to form a quaternary stereogenic center in high yield with high stereoselectivity. This finding extends the synthetic chemistry starting from β-keto sulfones.

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Highly enantio- and diastereoselective Mukaiyama-Michael reaction of 2-(phenylsulfonyl)cyclopent-2-en-1-one using enol silane of t-butyl thiopropionate is described. The product is formed in 87% yield with dr ratio of 27:1 and 91% ee under the stoichiometric conditions, and the yield, dr ratio, and ee were 89%, 49:1, and 88% ee, respectively, under the catalytic conditions. A highly stereoselective epimerization of the product of the Mukaiyama–Michael reaction which proceeds in 77% yield with dr ratio of 22:1 is described, too. Since both enantiomers of the ligand for this Mukaiyama-Michael reaction are available, a method for the synthesis of all four stereoisomers of the product as useful chiral building blocks has been established.