Kazuaki Okabe

Total synthesis of indole alkaloid pendolmycin

Abstract The teleocidin class of an indole alkaloid, pendolmycin (1) was synthesized from 1-(4-methylphenylsulfonyl)pyrrole in thirteen steps by way of the indole derivative (16), the amino- diester compound (6), and the ethyl carboxylate (5).

The second generation synthesis of a tumor promoter pendolmycin

Abstract Total synthesis of a tumor promoter pendolmycin (1) was accomplished in the stereospecific manner using a d -serine derivative 7 and an l -valine derivative 16 as chiral sources. Methyl 2-(bromomethyl)benzoate was used for the critical step of the indole cyclization 25 → 26 and 28.

Synthesis of teleocidins A, B and their congeners. Part 2. Synthesis of lyngbyatoxin A (teleocidin A-1), teleocidin A-2, pendolmycin, and (R, E)- and (S, E)-7-(3,7,11-trimethyl-1,6,10-dodecatrien-3-yl)-(−)-indolactams V☆

Abstract Details of the synthesis method of the tumor promoters, lyngbyatoxin A (= teleocidin A-1) ( 1 ) and teleocidin A-2 ( 2 ) from (R)- and (S)-methyl N-[7-(3,7-dimethyl-1,6-octadien-3-yl)-4-indolyl]-N-methyl-L-valinate ( 3 and 4 ) are presented. Other titled compounds, 6 , 7a , and 7b , were prepared analogously.

Synthesis of teleocidins A, B and their congeners. Part 3. Synthesis of dihydroteleocidin B-4 (dihydroteleocidin B), teleocidin B-3 and teleocidin B-4☆

Abstract Details of the synthesis method of the tumor promoters teleocidin B-3 (3), teleocidin B-4 (4) and dihydroteleocidin B-4 (9) (=dihydroteleocidin B) from (S)- and (R)-methyl N-methyl-N-[7-(3,6,7-trimethyl-1,6-octadien-3-yl)-4-indolyl]-L-valinates (20b and 20a) are presented.

Reactions of O,O-diprotonated nitro olefins with benzenes. Formations of phenylacetones, 4H-1,2-benzoxazines and biarylacetone oximes

Abstract O,O-diprotonated nitro olefins undergo three alternative electrophilic reactions which yield α-phenylacetones, 4H-1,2-benzoxazines and biphenylacetone oximes depending on the reaction conditions (temperature and time) and aromatic substrates. Although these reactions are seemingly divergent, a common intermediate of a phenylated protonated aci-nitro species, derived from the dication, is postulated to be involved in the reactions. Furthermore, the formation of benzoxazines and biphenylacetone oximes can be interpreted in terms of participation of novel chemical species with phenylethylene dication character derived from the common intermediate.

Pendolmycin, a new tumor promoter of the teleocidin A class on skin of CD-1 mice.

Pendolmycin, isolated from Nocardiopsis, is a compound structurally similar to teleocidin A, one of the 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐type tumor promoters. Pendolmycin has a C5 dimethyl allyl group attached to C‐7 of (‐)‐indolactam‐V, whereas teleocidin A has a C10 linalyl group attached to the molecule. The structure‐activity relationships of a hydrophobic moiety attached to (‐)‐indolactam‐V were studied in four compounds, (‐)‐indolactam‐V, pendolmycin, teleocidin A and newly synthesized 7‐(nerolidyl)‐(‐)‐indolactam‐V in tests on inhibition of the specific [3H]TPA binding to a particulate fraction of mouse skin, activation of protein kinase C and induction of both adhesion of HL‐60 cells and ornithine decarboxylase in mouse skin. The potencies of the compounds for these activities increased mainly depending on the length of the hydrophobic group. Pendolmycin had a tumor‐promoting activity on mouse skin initiated with a single application of 7,12‐dimethyl‐benz[a]anthracene, and its potency was just between those of (‐)‐indolactam‐V and teleocidin A. The role of the hydrophobic moiety is discussed with particular emphasis on the results obtained with 7‐(nerolidyl)‐(‐)‐indolactam‐V.

Total synthesis of dihydroteleocidin B-4 (dihydroteleocidin B)

Abstract A potent tumor promoter, dihydroteleocidin B-4 (=dihydroteleocidin B) ( 1 ) was synthesized from L -valine derivative 8 using an acid-catalyzed cyclization of 15 to 16 a to construct the teleocidin B structure unit.