The Claisen Rearrangement Using Carbohydrate Derivatives and Its Application to Natural Product Synthesis

1.The ortho-ester Claisen rearrangement(Johnson-Claisen rearrangement)is one of the highly stereoselective carbon-carbon bond forming reaction in current organic synthesis。Our interest is a pursuit of the highly stereoselective Claisen rearrangement reaction applied to carbohydrate-derived substrates for access to versatile chirons。The ortho ester Claisen rearrangement of Z-isomer of 3，5，6-trideoxy-1，2-OMICRON-isopropylidene-3-C-methyl-alpha-D-ribo-hept-5-eno-1，4-furanose with triethyl orthoacetate proceeded highly stereoselectively to form the major rearrangement product with(S)-newly introduced asymmetric center(9to1diastereoselectivity)。This product includes a1，3-dimethyl-2，4-diol substructure，and is expected to be a useful building block for such the macrolide synthesis(J.Carbohydrate Chem.，in press).2。The utility of the rearrangement product has been embodied through total synthesis of natural products such as(+)-asteltoxin.The subject of this Grant-in-aid is the total synthesis of(-)-acetomycin，an antimicrobial and antitumor agent。The starting material for the total synthesis was the major product obtained by the Claisen rearrangement of D-glucose derived allylic alcohol at C-3and triethyl orthopropionate。This first total synthesis of(-)-acetomycin established its absolute configuration。In the course of the total synthesis，one of the stereocongeners of the antibiotic，(+)-5-epi-acetomycin was also synthesized.From the minor product of the Claisen rearrangement，the other two stereocongeners，4-epi-，and 4，5-di-epi-acetomycin were synthesized by analogous reaction sequence adopted to the(-)-acetomycin synthesis。

1. The ortho-ester Claisen rearrangement (Johnson-Claisen rearrangement) is one of the highly stereoselective carbon-carbon bond forming reaction in current organic synthesis. Our interest is a pursuit of the highly stereoselective Claisen rearrangement reaction applied to carbohydrate-derived substrates for access to versatile chirons. The ortho ester Claisen rearrangement of Z-isomer of 3, 5, 6-trideoxy- 1, 2-OMICRON-isopropylidene-3-C-methyl-alphaーD-ribo-hept-5-eno-1, 4-furanose with triethyl orthoacetate proceeded highly stereoselectively to form the major rearrangement product with (S)- newly introduced asymmetric center (9 to 1 diastereoselectivity). This product includes a 1, 3-dimethylー2, 4-diol substructure, and is expected to be a useful building block for such the macrolide synthesis (J. Carbohydrate Chem., in press).2. The utility of the rearrangement product has been embodied through total synthesis of natural products such as (+)-asteltoxin. The subject of this Grantーinーaid is the total synthesis of (-)-acetomycin, an antimicrobial and antitumor agent. The starting material for the total synthesis was the major product obtained by the Claisen rearrangement of D-glucose derived allylic alcohol at C-3 and triethyl orthopropionate. This first total synthesis of (-)-acetomycin established its absolute configuration. In the course of the total synthesis, one of the stereocongeners of the antibiotic, (+)-5-epiーacetomycin was also synthesized. From the minor product of the Claisen rearrangement, the other two stereocongeners, 4-epi-, and 4, 5-di-epi-acetomycin were synthesized by analogous reaction sequence adopted to the (-)-acetomycin synthesis.