Pyrrolizidine alkaloids (July 1998 to June 1999)

Pyrrolizidine alkaloids

“…The synthesis of (ϩ)-australine 62 by White and Hrnciar via a tandem ring-closing metathesis-transannular cyclisation (RCM-TC) approach has now been reported in full. 13, 14 Romero and Wong have developed a short chemo-enzymatic approach culminating in the synthesis of australine 62, 7-epialexine 63, and 3-epi-australine 71, and which does not require protection of the hydroxy groups. 15 Beginning with 64, Sharpless asymmetric epoxidation using cumene hydroperoxide gave 65 which was rearranged, regioselectively ring opened with ammonia, and the nitrogen masked as the formate 66 (Scheme 11).…”

“…provided β-amino aldehyde 52, which upon hydrogenolysis afforded chysine B 53 as a single diastereomer, and then, on hydride reduction, isoretronecanol 54 (Scheme 9). Full details of an earlier synthesis of isoretronecanol 54 and of trachelanthamidine 55 have now been published 10,11. …”

Short Syntheses of (-)-( R )-Pyrrolam A and (1S)-1-Hydroxyindolizidin-3-one

“…Numerous pyrrolizidines were isolated from plants, a few from insects that feed on such plants and accumulate the bitter-tasting alkaloids as deterrents, but only a handful from molds. 1 In 1990 the Zeeck group reported the isolation of the so-called pyrrolams A-D from Streptomyces olivaceus (strain Tü 3082). 2 As distinguished from the more common and structurally more complex necine bases, the pyrrolams exhibit only moderate biological activity.…”

“…The resulting mixture was filtered through a short plug of Celite which was washed with MeOH (50 mL). The combined filtrates were concentrated on an oil pump to leave a yellow air-and moisture-sensitive oil (0.55 g, 99%) which was used right away without further purification; R f = 0.50 (CH 2 Cl 2 -MeOH, 19:1) 1. H NMR (CDCl 3 ): d = 1.49-1.65 (m, 1 H, 7-H), 1.85-2.06 (m, 3 H, 6-H, 7-H), 2.87 (dd, J = 21.4, 1.4 Hz, 1 H, 2-H), 3.02-3.12 (m, 1 H, 5-H), 3.27 (d, J = 21.4 Hz, 1 H, 2-H), 3.75-3.86 (m, 1 H, 5-H), 4.04-4.12 (m, 1 H, 7a-H).…”

“…dione [(R)-10]Crude (R)-10 (175 mg, 99%) was obtained as a yellow oil from (R)-9 (280 mg, 1.15 mmol) by the procedure described for compound (R)-5; R f = 0.52 (CH 2 Cl 2 -MeOH, 19:1) 1. H NMR (CDCl 3 ): d = 1.12-1.51 (m, 3 H, 6-H, 7-H, 8-H), 1.64-1.73 (m, 1 H, 6-H), 1.88-2.08 (m, 2 H, 7-H, 8-H), 2.61-2.73 (m, 1 H, 5-H), 2.90 (ddd, J = 22.1, 1.6, 0.9 Hz, 1 H, 2-H), 3.00 (ddd, J = 22.1, 2.0, 0.9 Hz, 1 H, 2-H), 3.70 (ddt, J = 11.9, 3.9, 0.9 Hz, 1 H, 8a-H), 4.35 (m, 1 H, 5-H).…”