Total Synthesis of the Didemnins; III. - Synthesis of Protected (2R,3S)-Alloisoleucine and (3S,4R,5S)-Isostatine Derivatives - Amino Acids from Hydroxy Acids

All articles of this category (2 S ,3 S )-2-Acetoxy-3-methylvaleric acid (3) is prepared from L-isoleucine (2) with 96% retention of configuration. Compound 3 is converted to optically pure methyl D-alloisoleucinate (7) as its hydrochloride salt, via the methanesulfonate 5 and the azide 6 with 76% yield and 99.9% inversion. Subsequent protection-saponification-activation of 7 , followed by reaction with the lithium enolate of methyl trimethylsilyl malonate and reduction, yields (3 S ,4 R ,5 S )- N -(9-fluorenylmethoxycarbonyl) isostatine (12) . (3 S .4 R ,5 S )-Isostatine is a characteristic unit of the didemnines 1 .