Hideki Miyazaki

Total synthesis of (±)-neoechinulin A, an indole alkaloid containing oxidized diketopiperazine

Abstract Protected neoechinulin A ( Z isomer) and its E isomer were synthesized by condensation of N-bis(methylthiomethyl)cyclo(Ala-Gly) with 2-(1,1-dimethyl-2-propenyl)-1-methoxymethylindole-3-aldehyde; deprotection of both isomers gave neoechinulin A, whose Z configuration was rigorously established. A novel cyclization of the protected neoechinulin A into a seven-membered cyclic compound was reported.

An efficient synthesis of platelet-activating factor (PAF) via 1-0-alkyl-2-O-(3-isoxazolyl)-SN-glycero-3-phosphocholine, a new PAF agonist utilization of the 3-isoxazolyloxy group as a protected hydroxyl.

Potent PAF agonists (R)-3a,b were synthesized and converted into PAF. Key steps include Mitsunobu reaction of a chiral secondary alcohol with 3-hydroxyisoxazole as the acidic component, and hydrogenolytic ring cleavage of the resulting 3-isoxazolyloxy group into the inverted alcohol.

Syntheses of 1-O-carboxyalkyl GLA-60 analogues

As part of our ongoing study to survey potent LPS antagonists, the following six compounds were synthesized in an efficient manner: 3-carboxypropyl and carboxymethyl 2-deoxy-2-(2,2-difluorotetradecanamido)-4-O-phosphono-3-O-[(R)-3- (tetradecanoyloxy)tetradecanoyl]-alpha- and beta-D-glucopyranosides (11 and 23; 32 and 36), as well as the non-fluorinated equivalents, carboxymethyl 2-deoxy-4-O-phosphono-2-tetradecanamido-3-O-[(R)-3-(tetradecano yloxy)- tetradecanoyl]-alpha-D-glucopyranoside (44) and carboxymethyl 2-deoxy-2-[(R)-3-(hydroxy)tetradecanamido]-4-O-phosphono-3-O-[(R)- 3- (tetradecanoyloxy)tetradecanoyl]-alpha-D-glucopyranoside (48). Of these compounds, 32 was most pronounced in terms of LPS-antagonistic activity.

Synthetic studies on fumitremorgin I. Synthesis of (±)-12-deoxy-12-epifumitremorgin B

Abstract Diketopiperazine derivative 5 containing an oxidized prenyl moiety was prepared. The aldol product of 5 and a functionarized indole-3-aldehyde 7 was a mixture of four stereoisomers which were converted to a single terahydro-β-carboline derivative 12-deoxy-12-epifumitremorgin B ( 2 ), in good yield.

Synthesis and absolute configuration of trehazolin aminocyclitol moiety

Optically active [1R-(1α,2β,3α,4β,5β)]-5-acetamide-1-acetoxymethyl-1,2,3,4-tetraacetoxycyclopentane 2 was synthesized from D-glucose. Compound 2 was identical in all respects with the hexaacetate derived from the natural trehazolin aminocyclitol moiety.