No abstract

in methanol for 24 h. The filtrate and washes were evaporated to dryness: yield 77 mg, 36% by weight; 127 wmol Val, 7.7 pmol Gly (yield 32%). Total 14C counts recovered in the filtrate indicated a yield of 36%. The solid was recrystallized from ether-petroleum ether. Paper electrophoresis at pH 1.5 gave a single radioactive spot at Rval 0.48 (standards of Gly-Val, Asp, and cyclic Dca-Val appeared at 0.86,0.74, and 0.66, respectively); 'H NMR (Varian HF, 220 MHz, MezSO-de) 6 0.91 (m, 6 H), 1.3-1.4 (broad m, cyclohexyl axial), 1.6-1.8 (broad m, cyclohexyl equatorial), 2.06 (m, 1 H, Val p-CH), 3.1 (m, tertiary CH), 4.1-4.2 (m,3 H, a-CH), 3.8 (~,3H,OCH3),7.32 (d,2H, J=8Hz,cyclohexyl NH), 7.68 (t, 1 H, J = 7 Hz, Gly NH), 8.64 (d, 1 H, J =: 8 Hz, Val XH); I3C NMR (Bruker HX-90, 22.6 MHz, proton decoupled,

No abstract

The biosynthesis of the antitumor antibiotic sibiromycin by Streptosporangium sibiricum requires the construction of four units: the amino sugar from glucose; the anthranilate ring from DL-tryptophan probably via kynurenine; the aromatic methyl group from methionine; the propylidene proline from L-tyrosine with the loss of two aromatic carbons and addition of a C-1 from methionine. Retention of tritium from DL-[5-3H]tryptophan in sibiromycin suggest an NIH shift during hydroxylation of an intermediate.

This paper descirbes biosynthetic labeling experiments on the conversion of tyrosine to the C2- and C3-proline units of anthramycin, tomaymycin, and sibiromycin. The biosynthetic fate of all of the aromatic and side-chain hydrogens has been determined in each antibiotic by using dual tagged (3H/14C) and 2H-labeled tyrosine molecules. In addition, experiments uing [15N]tyrosine and the tritiated D and L isomers of tyrosine have shed some light on the biochemical reactions which take place at tha alpha position of tyrosine. On the basis of results of all these experiments, a biosynthetic scheme had been proposed to rationalize the apparent inconsistencies which occur between the results for the three antibiotics. This scheme proposes that a common main pathway involving proximal extradiol cleavage of Dopa and condensation to form the pyrrolo ring leads ultimately to a C-7 branch point compound. Parallel pathways from this central branch point compound lead by well-known biochemical transformations to the C2-and C3-proline units of anthramycin, tomaymycin, and sibiromycin. The reactions in these parallel pathways are suggested to be "cosmetic or after events".