Nucleosteroids: Synthesis of purinyl-steroid derivatives under mitsunobu reaction conditions

Abstract

The feasibility of using the Mitsunobu reaction for coupling of purines with steroids to obtain nucleosteroids was investigated in the particular case of 6‐chloropurine and cholesterol. Three principal products were obtained: 3βbT‐(6‐chloropurin‐9‐yl)‐5‐cholestene (1), 3α‐(6‐chloropurin‐9‐yl)‐5‐cholestene (2), and 6βbT‐(6‐chloropurin‐9‐yl)‐3,5‐cyclocholestane (3), isolated with 10.5%, 22.7%, and 12.6% yield, respectively. The stereochemical and structural diversity of the coupling products are explained by the formation of a homoallylic carbocation through participation of the double bond of cholesterol.

New Purinyl-Steroid and Other Constituents from the Marine Fungus Penicillium brefeldianum ABC190807: Larvicidal Activities against Aedes aegypti

“…e 1 H-NMR spectrum (Table 1) of 1 in deuterated chloroform showed two purine hydrogen signals at δ [13] and adenine [14], which suggests that 1 is a hybrid of the two molecules. Considering that the C(3) ketocarbonyl carbon signal of the steroid nucleus is replaced by a new methine signal (δ H 5.32 (br dd, J � 5.2, 4.8 Hz); δ C 48.9), we inferred that the hybrid molecule was connected between C(3) of the steroid nucleus and N(9′) of the adenine moiety [15,16], and this deduction was further confirmed by heteronuclear multiple bond correlation . e chemical shift of C(3) (δ C 48.9 ppm (d)) revealed that the adenine moiety is α-oriented (axial direction) [15].…”

“…Considering that the C(3) ketocarbonyl carbon signal of the steroid nucleus is replaced by a new methine signal (δ H 5.32 (br dd, J � 5.2, 4.8 Hz); δ C 48.9), we inferred that the hybrid molecule was connected between C(3) of the steroid nucleus and N(9′) of the adenine moiety [15,16], and this deduction was further confirmed by heteronuclear multiple bond correlation . e chemical shift of C(3) (δ C 48.9 ppm (d)) revealed that the adenine moiety is α-oriented (axial direction) [15]. e stereochemistry of C(3) was further confirmed from the following nuclear Overhauser effect spectroscopy (NOESY) correlations (Figure 3): H(8′) ⟷ H(1α)/H(2α), H(1α) ⟷ H(9), and H(2β) ⟷ Me-18.…”

Synthesis of ferrocenyl conjugates of thio analogs of hydroxyl-containing biomolecules via the Mitsunobu reaction with N-(ethoxycarbonyl)ferrocenecarbothioamide as the pronucleophile

“…It is worth noting here that Mitsunobu reactions of cholesterol lead in some cases to mixtures of products, resulting from assistance from the ethylenic bond, 10 although examples of the selective C-3 substitution with inversion of the configuration are also known. 11 A cyclic voltammetry study of 3 in dichloromethane solution showed that this compound undergoes reversible one-electron oxidation at 254 mV (vs Fc + /Fc) with DE = $70 mV.…”