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

Abstract

A synthesis of 16,17-dihydrosecodin-17-ol and of secodine is described. Various indole derivatives were elaborated to a series of pyridinium salts, potential precursors for 1,2- and 1,6-dihydropyridine compounds exemplifying the proposed biointermediate 'dehydrosecodine.'

Dihydropyridines in synthesis and biosynthesis. IV. Dehydrosecodine, in vitro precursor of indole alkaloids

“…Reaction with N-bromosuccinimide in pyridine followed by displacement with cyanide gave nitrile 33 and, after methanolysis, the bromo ester 34. Alkylation of 3-ethylpyridine gave the required salt 26 (in 10% overall yield from phenylhydrazine (Scheme 7)) analogous to the iodide and chloride salts prepared earlier (5,6).…”

“…Scheme 1 illustrates the proposed possible biosynthetic pathway from stemmadenine 1 (a member of the Strychnos family) to catharanthine 2 (Iboga) and vindoline 3 (Aspidosperma). Direct evidence for an intermediate of type "A" (Scheme 1) has been provided via a series of experiments conducted in these laboratories (4)(5)(6) and summarized in Scheme 2. Thus, variously labelled forms of secodine 4 were incorporated intact into the alkaloids catharanthine 2, vindoline 3, vincamine 5, and apparicine 6.…”

“…Alternatively, thermolysis of 23 gave 22 again, presumably via 4 (1 1). Indeed separate syntheses of secodine 4 have been described (5,12).…”

Total synthesis of N a-methylsecodine

“…Methyl iodide (5.0 ml, 0.09 mol) was added dropwise to the reaction mixture which was then kept overnight at 25 "C. Excess of sodium hydride was carefully destroyed with water. The aqueous layer was acidified and extracted exhaustively with ethyl acetate and the extracts were dried over anhydrous sodium sulphate and evaporated to give the acid (4) a reddish brown gum Methyl N-Methylindole-3-acetate (5).--N-Methylindole-3acetic acid (4) (4.0 g, 0.021 mol) was dissolved in anhydrous methanol (200 ml) and sulphuric acid (2.0 ml) was added. The solution was stirred for 24 h at 25 "C and was then evaporated to give a brownish gum.…”

“…The aqueous solution was extracted with dichloromethane (3 x 20 mi), and the combined extracts (60 ml) were washed with water, dried with sodium sulphate, and concentrated under reduced pressure to afford a pale orange gum (1.5 (2), 67 (2), and 55 (6); G(CDC13) 2.02 (2 H, q, J 7.0 Hz, CHzCH3), 3.72 (3 H, s, NCH3), 5. 5 (1 H, m, C=CH),and 6.8 (1 H, s, indole 2-H).…”