1. N-(Fluoren-9-ylmethoxy-carbon-yl)-l-isoleucine
Kazuhiko Yamada, Daisuke Hashizume, Tadashi Shimizu, Kenzo Deguchi Acta Crystallogr Sect E Struct Rep Online. 2008 Jul 19;64(Pt 8):o1533. doi: 10.1107/S1600536808021855.
In the crystal structure of the title compound [systematic name fluoren-9-ylmethyl N-(1-carb-oxy-2-methyl-butyl)carbamate], C(21)H(23)NO(4), the mol-ecular plane of the O=C-NH-C(α) unit is slightly pyramidalized. The N atom deviates from the basal plane by 0.2086 (12) Å. The O=C-N-C(α) torsion angle is -17.2 (2)°, and the C-N and O=C bond lengths are 1.3675 (17) and 1.2122 (17) Å, respectively. Apparently the character of the sp(2) hybrids of the mol-ecular plane is, to some extent, reduced. The crystal structure exhibits two inter-molecular hydrogen bonds (O-H⋯O and N-H⋯O), in which the hydr-oxy O atom acts as a donor to the carbonyl group and an acceptor of the amide group, respectively.
2. Biogenetic origin of the D-isoleucine and N-methyl-L-alloisoleucine residues in the actinomycins
T Yajima, K Mason, E Katz Antimicrob Agents Chemother. 1976 Feb;9(2):224-32. doi: 10.1128/AAC.9.2.224.
Studies with (14)C-labeled isoleucine stereisomers have established that l-alloisoleucine, d-alloisoleucine, and d-isoleucine may function as precursors for the biogenesis of d-isoleucine and N-methyl-l-alloisoleucine residues in actinomycin. l-[(14)C]isoleucine appears to be employed chiefly for d-alloisoleucine (and N-methylisoleucine [?] formation); however, its role in the biosynthesis of d-isoleucine and N-methylalloisoleucine remains unclear. The potential pathway of biosynthesis of d-isoleucine and N-methyl-l-isoleucine is discussed.
3. Formation of L-alloisoleucine in vivo: an L-[13C]isoleucine study in man
P Schadewaldt, A Bodner-Leidecker, H W Hammen, U Wendel Pediatr Res. 2000 Feb;47(2):271-7. doi: 10.1203/00006450-200002000-00020.
L-alloisoleucine (2S, 3R), a diastereomer of L-isoleucine (2S, 3S), is a normal constituent of human plasma. Considerable amounts accumulate in maple syrup urine disease, in which the branched-chain 2-oxo acid dehydrogenase step is impaired. The mechanism of L-alloisoleucine formation, however, is unclear. We addressed this issue by performing oral L-[1-13C]isoleucine loading (38 micromol/kg body wt, 50% 1-13C) in overnight-fasted healthy subjects (n = 4) and measuring the 3-h kinetics of 13C-label incorporation into L-isoleucine plasma metabolites. Compared with L-isoleucine, the time course of 13C-enrichment in the related 2-oxo acid, S-3-methyl-2-oxopentanoate, was only slightly delayed. Peak values, amounting to 18+/-4 and 17+/-3 mol percent excess, respectively, were reached within 35 and 45 min, respectively. The kinetics of 13C-enrichment in S- and R-3-methyl-2-oxopentanoate enantiomorphs were similar and linearly correlated (p << 0.001). In L-alloisoleucine, however, 13C-label accumulated only gradually and in minor amounts. Our results indicate that R-3-methyl-2-oxopentanoate is an immediate and inevitable byproduct of L-isoleucine transamination and further suggest that alloisoleucine is primarily formed via retransamination of 3-methyl-2-oxopenanoate in vivo.
