Polonovski transformation of (+)-nupharidine. Stereochemistry and utility in synthesis

Abstract

tion was quenched with a solution of bromobenzene in toluene, giving a deep-red solution. After addition of saturated aqueous ammonium chloride the ammonia was removed by evaporation. The residue was diluted with water, extracted with ethyl acetate, and the extracts were dried, filtered, and concentrated in vacuo to give an oil. This was dissolved in chloroform and filtered through Florisil (2 g). Elution with chloroform removed less polar impurities and elution with 25% ethyl acetate-chloroform yielded 40 mg of a 2:1 mixture of ketones 24 and 35. Separation by preparative tic (silica gel PF254) developed twice, 10 cm with 20% ether-methylene chloride) afforded 10 mg (25 %) of ketone 35, whose ir was identical with that of authentic material, and 18 mg (47%) of ketone 24, mp 156-158°, identical by its ir spectrum with an authentic sample.Tetracyclic Formamide 39. To an ice-bath-cooled solution of the ketone 35 (30 mg, 0.1 mmol) in methylene chloride (40 ml), boron trifluoride etherate (0.35 ml) was slowly added and the resulting red solution was stirred 11 hr at room temperature. The solution was poured onto cold, saturated ammonium chloride, neutralized with solid potassium carbonate, and extracted with methylene chloride. The extracts were dried, filtered, and concentrated in vacuo to give a glass which was dissolved in 50% benzenechloroform and filtered through Florisil (0.5 g). Elution with additional solvent and concentration of the filtrate yielded a glass which crystallized from ether to give 20 mg (72%) of the amide 39. An analytical sample was recrystallized from ethyl acetate-cyclohexane: mp [264][265][266] ir (CHC13)

Crystal structure, absolute configuration and stereochemistry of nupharidine hydrobromide

“…At the outset of this analysis, it was not clear from chemical work (LaLonde et al 1971) whether nupharidine possessed a transfused or a cis-fused quinolizidine N-oxide system. The present X-ray analysis clearly established that (a) the quinolizidine N-oxide system is built of two cisfused six-membered rings in chair conformations and (b) the methyl and the furan substituents occupy the equatorial position, with the plane of the furan ring nearly normal to the C(4)---N(5) bond.…”

“…The selective conversion of the quinolozidine type Nuphar alkaloid, deoxynupharidine, to A 6-dehydrodeoxynupharidine was of interest in connection with biogenetic and mass spectral studies (LaLonde et aL 1971). The naturally occurring N-oxide nupharidine was regarded as a possible starting point to achieve the selective introduction of a double bond into ring B at the C-6 position.…”

“…Though the desired reaction was realized in good yield, additional work on the rate of oxidation of deoxynupharidine and 7-epideoxynupharidine suggested that the quinolizidine N-o~ide system in the former might be cis-fused (LaLonde et aL 1971). In order to'establish this point, an X-ray study was undertaken.…”

Synthesis of α-thiohemiaminal derivatives of deoxynupharidine

“…A CH2C12 solution of 6dehydro-deoxynupharidine (I), freshly prepared from nupharidine (16), and an equal mole or one mole excess of thiating agent was flushed with N,, sealed, and kept in the dark at 25OC until tlc showed no further increase in the relative amount of aarylthiohemiaminal to starting amine. Unconverted enamine, 3, and 2 ascended the plate in every case in the order just given.…”

Electron‐impact mass spectrometry of Nuphar alkaloids

“…Of these, m/e 98 and 97 are retained in the mass spectrum of the ring A singly labeled DON (V)* but are shifted two mass units higher* in the spectrum of the ring B doubly labeled DON (V1). 2 In contradistinction, m/e 136 and 94, and m/e 107 and 81, the Thus the group of peaks m/e 136, 107,98,97 and 81 containing the four dominant peaks of the mass spectrum arise through cleavage of ring A, which reasonably is made relatively labile to fragmentation by the 3-fury1 group at C-4 and the methyl group at C-1. As will be seen elsewhere in this paper, fragmentation in ring B becomes competitive only when a C-7 alkylthio group is added to the basic DON skeleton.…”