Two Pyrrolo[1,2‐a]azepine Type Alkaloids from Stemona collinsaeCraib: Structure Elucidations, Relationship to Asparagamine A, and a New Biogenetic Concept of Their Formation

Abstract

The alkaloids 1',2'-didehydrostemofoline (2) and 2'-hydroxystemofoline (3) from Stemona collinsae Craib (Stemonaceae) were studied by X-ray crystallography and NMR spectroscopy, and they are compared with the parent compound stemofoline (1). The X-ray analysis of the CH2Cl2 solvate of 2'-hydroxystemofoline (3) allowed the determination of the absolute configuration of this compound unequivocally, whereas optical rotation was used to infer the absolute configuration of 1',2'-didehydrostemofoline (2). Based on these results, it is shown that asparagamine A isolated from Asparagus racemosus Willd. (Asparagaceae) is identical to 1',2'-didehydrostemofoline obtained from S. collinsae Craib, and that the reported plant source of asparagamine A was most likely a Stemona species. In the context of the current investigations, a novel concept on the biosynthesis of Stemona alkaloids has been worked out and is presented here.

Application of an intramolecular dipolar cycloaddition to an asymmetric synthesis of the fully oxygenated tricyclic core of the stemofoline alkaloids

“…Support for the rationale of C2-epimerization at the iminium stage of the reaction was obtained by in situ NMR monitoring of the O-triflation process of the trans-substituted vinylogous amide 19 (Scheme 5) in CDCl 3 . Clean formation of the corresponding vinylogous iminium triflate was observed within 1 hr, providing a 4:1 mixture of the trans-and cis-iminium triflates 20 and 21, respectively.…”

“…After cooling to room temperature, the resulting orange suspension was transferred to a separatory funnel containing deionized water (300 mL) and extracted with dichloromethane (3 x 300 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo providing 5-hydroxymethyl-2,2-dimethyl- [1,3] dioxolane-4-carboxylic acid trimethylsilanylmethyl-amide (7.8 g, 97%) as a brown solid which was used without further purificaion. R f = 0.16 (33% ethyl acetate in hexanes); 1 NO 4 Si (MH + ) 262.1474, observed 262.1471.…”

“…R f = 0.16 (33% ethyl acetate in hexanes); 1 NO 4 Si (MH + ) 262.1474, observed 262.1471. To a solution of 5-hydroxymethyl-2,2-dimethyl- [1,3]dioxolane-4-carboxylic acid trimethylsilanylmethylamide (4.0 g, 15.3 mmol, 1.0 equiv) in dimethylsulfoxide (30 mL) was added triethylamine (15 mL, 107 mmol, 7.0 equiv). Sulfer trioxide-pyridine complex (9.7 g, 61 mmol, 4.0 equiv) was added via cannula in a solution in dimethylsulfoxide (30 mL).…”

“…After stirring at room temperature for 26 hours, the reaction was quenched with saturated aqueous sodium bicarbonate (1 mL) and the mixture transferred to a separatory funnel containing deionized water (50 mL). Following extraction with dichloromethane (3 x 100 mL) the combined organic extracts were dried over sodium sulfate, filtered, concentrated in vacuo, and purified by silican gel column chromatography (20% ethyl acetate in dichloromethane), affording (2,2-Dimethyl-6-oxo-5-trimethylsilanylmethyl-tetrahydro- [1,3]dioxolo [4,5- [4,5-c]pyrrol-4-yl)-acetic acid ethyl ester (2.38 g, 7.22 mmol, 1.0 equiv) in THF (130 mL) was added 1.0 M aqueous lithium hydroxide (21.7 mL, 21.7 mmol, 3.0 equiv). After stirring at room temperature for three hours the resulting pale yellow suspension was transferred into a separatory funnel containing 500 mL 0.5 M aqueous hydrochloric acid.…”

“…R f = 0.20 (ethyl acetate); 1 2-(2,2-Dimethyl-6-thioxo-5-trimethylsilanylmethyl-tetrahydro-[1,3]dioxolo[4,5-c] pyrrol-4-yl)-N-methoxy-N-methyl-acetamide (43) A solution of lactam 42 (1.68 g, 5.57 mmol, 1.0 equiv) in toluene (56 mL) was charged with Lawesson's reagent (1.24 g, 3.07 mmol, 0.55 equiv), sealed and heated to 65 °C for 16 hours. The resulting pale yellow solution was concentrated in vacuo and purified directly by silica gel column chromatography (dichloromethane followed by 3% acetic acid in ethyl acetate) to afford (2,2-Dimethyl-6-thioxo-5-trimethylsilanylmethyl-tetrahydro- [1,3] To a solution of 43 (607 mg, 1.68 mmol, 1.0 equiv) in acetonitrile (34 mL) was added 1-bromo-2-butanone (180 μL, 1.77 mmol, 1.05 equiv) at room temperature. After 22 hours, triphenylphosphine (485 mg, 1.85 mmol, 1.1 equiv) was added followed by triethylamine (260 μL, 1.85 mmol, 1.1 equiv).…”