An improved route to pregna-5,20-dien-3β-ol (muricin aglycone): Carbon and proton nuclear magnetic resonance assignments for the aglycone and a number of related pregnene derivatives

Abstract

Carbon and proton assignments for muricin aglycone (5) and a number of related pregnenes, carried out with the aid of two-dimensional homo- and heteronuclear chemical shift correlation experiments, have resulted in previously reported carbon assignments for the aglycone being revised. An improved route to muricin aglycone is also reported.

Cyclobutanone Approach to the Synthesis of Cardenolides

“…Starting olefin 1 , 3β‐acetoxypregna‐5,20‐diene,18 was obtained from the commercially available 3β‐acetoxypregn‐5‐en‐20‐one following the procedure reported earlier 19. We found, however, that reduction of this ketone with sodium borohydride in methanol gave a mixture of the alcohols (20 R )‐ 2 19 and (20 S )‐ 3 20 in a 9:1 ratio, as estimated by the integration of the 1 H NMR signals at δ = 0.76 and 0.67 ppm, respectively, arising from the 18‐CH 3 group. The mixture of 2 and 3 ,which gave two distinct spots on TLC plates, was used without separation in the next step.…”

“…The mixture of 2 and 3 ,which gave two distinct spots on TLC plates, was used without separation in the next step. Mesylation in pyridine/dichloromethane gave the productasa mixture of chromatographically indistinguishable isomers 4 [ δ H = 0.79 (singlet due to the 18‐CH 3 group) and 3.00 (singlet due to the CH 3 SO 2 group)]19 and 5 ( δ H = 0.72 and 2.98). The mesylates were eliminated by treatment with potassium tert ‐butoxide in refluxing toluene to give the diene 1 19.…”

“…Mesylation in pyridine/dichloromethane gave the productasa mixture of chromatographically indistinguishable isomers 4 [ δ H = 0.79 (singlet due to the 18‐CH 3 group) and 3.00 (singlet due to the CH 3 SO 2 group)]19 and 5 ( δ H = 0.72 and 2.98). The mesylates were eliminated by treatment with potassium tert ‐butoxide in refluxing toluene to give the diene 1 19. The 6β‐methoxy‐3α,5‐cyclo‐5α‐pregn‐20‐ene 6 ,21 with a protected Δ 5 double bond, was then used as the substrate for the preparation of the cyclobutanone by reaction with a ketene.…”

“…3β‐Acetoxy‐21,21‐dichloro‐21,23‐cyclo‐24‐nor‐20ξ‐chol‐5‐en‐23‐one (7): A solution of trichloroacetyl chloride (213 mg, 1.16 mmol) in anhydrous diethyl ether (7.5 mL) was added dropwise over 2 h to a suspension of 3β‐acetoxypregna‐5,20‐diene ( 1 )19 (200 mg, 0.58 mmol) and zinc dust (114 mg, 1.74 mmol) in anhydrous diethyl ether (7.5 mL) under argon. During the addition of trichloroacetyl chloride, the reaction mixture was irradiated in the water bath of a sonicator at a bath temperature of 25–30 °C.…”

Solid‐state nuclear magnetic resonance investigation of neurosteroid compounds and magnesium interactions

“…1 H and 13 C chemical shifts (see Table S2) and the m.p. were consistent with that of the 20( R ) form reported in the literature …”