Statine, asymmetric synthesis

A-Boc-leucinal may react with allyl- and alkenyhnagnesium hahdes giving syn- and awf/-products in ca 9 1 ratio. This method was used for the asymmetric synthesis of important amino acids like statine and norstatine. An enantioselective desymmetrization of anhydrides was reported. Arylmagnesium chlorides react in toluene in the presence of (—)-sparteine (1 equiv.) with 3-substituted glutaric anhydrides 215, giving aryl ketones with 87-92% ee (equation 145). ... 

In Masamune s initial synthesis of the C -Cn polyacetate region of the bryo-statins (Scheme 9-37), the chiral reagents (S)- and (R)-53 were used to control the stereocenters at C3, C7 and Cn [36], The first of these reactions used R)-53 to set the C3 center in 115 and then two subsequent double asymmetric induction aldol reactions, to give 116 and 117, set the remaining stereocenters. 

In the previous synthesis, two asymmetric aldol reactions using dienyl silyl ethers were described, one using a chiral Lewis acid for stereoinduction while the other used substrate control from a chiral aldehyde. This can be compared with the use of chiral dienolate 131 in the synthesis of a Ci-Cie fragment of the bryo-statins (Scheme 9-41) [59J. Here, the menthyl-derived auxiliary is covalently attached to the enolate, and again an excellent level of asymmetric induction was achieved on addition to aldehyde 132 to give adduct 133. 

Hydroxyalkyt and Epoxyalky Acids. The reaction of aldehydes or ketones with dialkyl hydrogenphosphonate continues to be widely used for the synthesis of a-hydroxyalkylphosphonates ° and magnesium oxide has been reported to be an effective catalyst for the reaction. The reaction has been used in enantioselective synthesis. For example, in the preparation of chiral a, -dihydroxyphosphonic acids 171 and 172 (Scheme 14), with preferential formation of the jyn-isomer 171, and the statin analogue 2-amino-1-hydroxy-3-phenylpropylphosphonic acid (173) (Scheme 15). Catalytic asymmetric... 

Silyl ketene acetal adds photolytically to C50 give a-fullerene-substituted carboxylic esters and are used in L-quebrachitol and statine synthesis They induce the first highly asymmetric Pummerer-type reaction of acyclic sulphoxides, giving siloxy(arylthio)alkanes with >99% ee541. 

Asymmetric Hydrogenation of Keto Esters in the Total Synthesis Statins ° are effective inhibitors of 3-... 

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