Biosynthesis of the indole alkaloids

Abstract

CHEMISTRY: MONEY ET AL. 901discussed with respect to the possibilities of reducing or augmenting antigenicity, modifying protein properties, and permanently attaching drugs to receptor sites. Potential applications to the treatment of cancer, organ transplantation, production of antibodies to viruses, treatment of sickle-cell anemia, myasthenia gravis, phenylketonuria, and mental illness have been mentioned. The usefulness of protein transformation in the investigation of receptor sites has been pointed out.The author would like to thank Nechama S. Kosower of the Department of Medicine, Albert Einstein College of Medicine, Yeshiva University, for many useful and critical discussions.* Supported in part through grant GP-251 from the National Science Foundation.f Alfred P. Sloan fellow, 1960-1964. 1 Kosower, E. M., these PROCEEDINGS, 51, 1141PROCEEDINGS, 51, (1964. 2Hunter, M. J., and M. L. Ludwig, J. Am. Chem. Soc., 84, 3491 (1962 March 3, 1966 Numerous theories regarding the biosynthesis of the Yohimbe, Strychnos, and Cinchona alkaloids have been propounded. '-5 In each of these hypotheses, condensation of tryptophan (or tryptamine) with various C9-Cjo units is invoked to rationalize the diversity of structure found in these bases, conveniently summarized in the pattern (Fig. 1, I). Incorporation experiments6 have demonstrated that administration of tryptophan-2-C14 to Rauwolfia serpentina plants leads to ajmaline-5-C" (II). However, in spite of numerous feeding experiments,7 8 the origin of the Cg-Cio unit remains obscure. Thus, radioactive tyrosine, alanine, and mevalonic acid when fed to R. serpentina were not incorporated7 to any significant extent into ajmaline. These results seemed to invalidate those hypotheses requiring intervention and subsequent fission ----) of the units III, IV, and V which,

Chemistry and Biology of Biosynthetic Diels–Alder Reactions

“…By 1970, Scott had elucidated a significant portion of the biosynthetic pathway through hydroponic feeding experiments with Vinca rosea shoots. [117] These results along with chronological isolation studies led to the proposed biosynthetic pathway outlined in Scheme 50. The intermediacy of 271 was invoked to explain the incorporation of stemmadenine (272) into both catharanthine (273, iboga skeleton) and into vindoline (274, aspidosperma skeleton).…”

Developmental and Light Regulation of Desacetoxyvindoline 4-Hydroxylase in Catharanthus roseus (L.) G. Don.1

“…These alkaloids are dimers formed from the condensation of catharanthine and vindoline (Svodoba and Blake, 1975). Early studies have shown that the pattern of alkaloids extracted from C. roseus seedlings was greatly affected by development and light (Mothes et al, 1965;Scott, 1970). Etiolated seedlings contained high levels of the late vindoline precursor tabersonine, which upon illumination was transformed stoichiometrically into vindoline (Balsevich et al, 1986;De Luca et al, 1986).…”

“…Etiolated seedlings contained high levels of the late vindoline precursor tabersonine, which upon illumination was transformed stoichiometrically into vindoline (Balsevich et al, 1986;De Luca et al, 1986). In contrast, catharanthine, which accumulated to high levels in etiolated seedlings, was hardly affected by the light regime (Scott, 1970;Balsevich et al, 1986). These studies suggested that light is a major limiting factor in the conversion of tabersonine to vindoline and in the formation of dimeric indole alkaloids (Balsevich et al, 1986;De Luca et al, 1986, 1988.…”

Dihydropyridines in synthesis and biosynthesis. I. Secodine and precursors of dehydrosecodine

“…The crude tosylate 56 (41 mg) and lithium iodide (158 n~g ) were heated in refluxing, dry acetone (15 mL) for 19 h. The solvent was evaporated and the residue chromatographed on silica gel to yield 57 (35 mg, 947,); 'Hmr 6 : 6.9-7.7 (9H, m, aromatic-H), 6.80 (lH, d, J = 2 Hz, olefinic-H), 5.90 (1H, d, J = 2 Hz, olefinic-H), 5.22 (2H, bs, -NCH,C,H,), 3.52 (3H, s, -OCH,), 3.34 (4H, bs, -CH2CH,-); ms m'e: 445 (M+), 318, 304, 149, 91.…”

“…Wenkert (2) first speculated that such intermediates could be involved in the later stages of Aspidosperl?la and Iboga alkaloid biosynthesis and experimental evidence supporting such a proposal calne forth from various investigations in different laboratories. Scott's experinlents with germinated Catharantl?~~~ i.oseus seedlings (3)(4)(5) and our own studies with C. rospus plants ( 6 ) brought forward a rationale (Scheme 1)bvhich i~lvoked such systerus (e.g., 'intermediate A'). Clearly such studies suggested, but did not prove, the role of dihydropyridines in these biosynthetic pathways.…”