22,26-Epiminocholestane

Hapepunine (72), occurring in Fvitillavia aamtsahataensis, is the first natural 166-hydroxy-22,26-epiminocholestane derivative encountered (Mitsuhashi et al., Tetrahedron Letters, 1978, 2099). Anrakorinine, from the same source, affords a tosylate which on reduction (LiAlH ) yields hapepunine (72). In its pmr-spectrum it lacks a methyl singlet at 6 0.96 ppm (present in hapepunine), but has an AB quartet (2H) at 3.62 and 3.88 ppm. Consequently it is formulated as 18-hydroxyhapepunine (73) idem, Phytochem., 1981, M, 157). Several indolizidine bases, also related to Solarium Alkaloids, have been encountered in the Fritil-laria group. Camtschatcanidine, for example, from F. aamtsohatoensis, is (74), on the basis of spectral comparison with solanidine on reduction (LiAlHi ) of its 0-tosyl-derivative solanidine (75) is formed (Mitsuhashi et al.. 

Veralkamine and veralinine are regarded as derivatives of the rearranged steroid hydrocarbon cholestane (5). However, there are also alkaloids possessing a normal cholestane skeleton (the 22,26-epiminocholestanes cf. Vol. X, p. 60). 

Veralozidine (97) (C27H43NO2 mp 153-155° [a] —92.2° in ethanol) was isolated from the green part of Veratrum lobelianum 69). The mass spectrum of veralozidine exhibited a fragmentation pattern indicative of a 22,26-epiminocholestane skeleton. The UV spectrum of this alkaloid showed a maximum attributable to the C=N double bond. Veralozidine displayed IR absorption due to a hydroxy, a 3jS-hydroxy-5-ene, and a C=N group. 

Veralkamine (104) is the first member of a steroidal alkaloid type with an 18-TCor-17j8-methyl-22,26-epiminocholestane skeleton. Its complete structure and stereochemistry have been established by recent chemical and physicochemical reinvestigation 70, 71), including X-ray structural analysis 72). Its steroidal nature was demonstrated by selenium dehydrogenation. The base 104 was further characterized by... 

Veralinine, a minor alkaloid from Veratrum album subsp. lobelianum, also has the rearranged 22,26-epiminocholestane skeleton (74). From chemical and spectroscopic evidence this Veratrum base is regarded as (22S,25S)-22,26-epimino-17/3-methyl-18-Jior-cholesta-5,12-dien-3 iS-ol (118). This structure was confirmed by correlation with veralkamine. The ketone 115 prepared from veralkamine was treated with ethanedi-thiol. Desulfurization of the resultant thioketal 119 with Raney nickel yielded the C-16 deoxo compound 120, which is identical with (22S,25S)-22,26-acetyl-epimino-17 3-methyl-18-7ior-5a,13a-cholestan-3j8-ol, also prepared from veralinine (118) via catalytic hydrogenation... 

It was reported earlier that 16g-hydroxy-22,26-epiminocholestane derivatives such as solaverbascine (16) were oxidised smoothly by manganese dioxide to yield spirosolane derivatives such as sola-... 

The hydroxy-group absorption in the i.r. spectra of 16-hydroxylated 22,26-epiminocholestanes has been examined." Absorption maxima consistent with seven-membered-ring hydrogen bonding between the amino-function and hydroxy-group at C-16 was observed for both the 16a- and 16 -series. The i.r. absorptions of several acetylated derivatives were also studied. 

The mass spectral fragmentations of backbone-rearranged steroids of the type (60) and the related A " -olefins are characteristic and dependent upon the configuration of the side-chain. Mass spectral fragmentation patterns are reported for a number of steroidal oximes, and for 5a-chloro-6j5-nitro-steroids, for a series of 22,26-epiminocholestane derivatives, and for 5a- and 5j5-3,6-diones. The mass spectrometry of cardenolides has been reviewed. ... 

Extraction of Fritillaria camtschatcensis, a known source of solanidine, has yielded tomatidenol (34), solasodine (16a), and a new alkaloid hapepunine, C2sH47N02. Hapepunine was assigned the N-methyl 22,26-epiminocholestane structure (35 a) on the basis of spectroscopic studies similar to those described above for teinemine. This structure proposal was proved by the partial synthesis of hapepunine from tomatidenol (34) via the desmethyl derivative (35b). Hapepunine (35 a) is the first natural 16j8-hydroxy-22,26-epiminochoIestane derivative. ... 

Epiminocholestanes (16,28-secosolanidanes) The alkaloids of this group can be assigned to two main... 

Epiminocholestanes. Alkaloids with this structure are intermediates in the biosynthesis of spirosolane, so-lanidine, a-epiminocyclohemiacetal, and 3-aminospirostane alkaloids. (25R)-26-Aminocholesterol (68) is precursor to the 22,26-epiminocholestanes. The biosynthesis of verazine (47), etioline (66), and solacongestidine (65) is discussed above. 

L Ssriaquidiiie. From green berries of Solanum pseudoquina, solaquidine was isolated. The H-NMR spectrum indicates two methoxy groups 3.10 and 3.15 ppm). The — 1 in the MS is found at mje 444 the base peak at m/e 98 shows the presence of a methylpiperidine side chain (see Table VI). Two abundant fragments, mje 101 and 127, indicate that both methoxy groups are located at C-3. A 3,3-dimethoxy-22,26-epiminocholestane structure (48) was assumed for solaquidine. The absolute configurations at C-5, C-22, and C-25 remain undetermined 108). 

Solanopubamide B 22,26-Epiminocholestanes (solacongestidine type) 3-Hvdroxv-22.26-epimi-nocholestanes 3 (AO-Acetyl derivative of solanogantamine One basic centre S. pubescens WnxD. (3)... 

S. seaforthianum Andr., St Vincent lilac alkaloids solanoforthine (3-amino-a-epiminocyclohemiketal), solaseaforthine, isosolaseaforthine (3-amino-22,26-epiminocholestanes) (Table 7.3, Fig. 7.20)... 

Saracha punctata Ruiz Pav. Sarachine (3 3-amino-22,26-epiminocholestane-type) (7)... 

An alternative pathway was proposed for 22ocA(-spirosolanes, e.g., solasodine (pathway B in Fig. 7.24). Incorporation studies with labelled potential precursors administered to S. laciniatum indicated that the introduction of nitrogen occurs immediately after the hydroxylation at C-26 [forming (251 )-26-aminocholesterol] and before a further oxidation of the side chain. Afterwards, probably oxygenation of C-22 takes place as a prerequisite for the formation of ring F. Incorporation studies with the labelled 22,26-epiminocholestane solacongestidine (Fig. 7.19) and its... 

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