9 Syntheses of Ungiminorine and Related Alkaloids
Details
Ungiminorine, one of the highly oxygenated Amaryllidaceae alkaloid of lycorine type, has been elucidated as (3) on analogy with the structure of narcissidine (1). We transformed lycorine (5) into ungiminorine (3) in a stereospecific manner thus accomplishing its total synthesis in formal sence. 1. Synthesis of Demethylungiminorine Short treatment of diacetyllycorine (7) with neutral permanganate in acetone-water afforded the glycol-lactam (9) in moderate yield, which gave the triacetate (11) on acetylation. The stereochemistry of the glycol function was determined by detailed analysis of their H-NMR spectra (Fig. 2) which indicated that J_<H_2-H_3> changed from 10Hz in (9) into 〜0Hz in (11). This change is available only when the glycol function has α-configuration and the conformation at ring C changed from the distorted boat in (9) into the distorted chair form in (11). Warming the triacetate (11) with SOCl_2-pyridine effected the desired dehydration to yield the Δ^<3α,4>compound (13) which on LAH reduction gave demethylungiminorine, m.p. 210° (dec.) 2. Synthesis of Ungiminorine Treatment of 1-acetyllycorine (18) with POCl_3-HCl gave the chlorohydrin acetate (19) in excellent yield, which gave hippamine on treatment with K_2CO_3-MeOH or NaOMe via lycorene-oxide (17). Permanganate oxidation of acetylhippamine (20) as above yielded the glycol-lactam (21) which on acetylation and dehydration with SOCl_2-pyridine followed by LAH reduction gave ungiminorine (3), m.p. 206-208°(dec.)
