Almagro Luis, Nogueras Manuel, Suárez Margarita, Cobo Justo, Glidewell Christopher
Departamento de Química Inorgánica y Orgánica, Universidad de Jaén, 23071 Jaén, Spain.
Laboratorio de Síntesis Orgánica, Facultad de Química, Universidad de la Hbana, 10400 La Habana, Cuba.
Acta Crystallogr C Struct Chem. 2018 Dec 1;74(Pt 12):1667-1673. doi: 10.1107/S2053229618015887. Epub 2018 Nov 21.
Two new functionalized steroids containing both chloro and formyl substituents in ring A, and intended as precursors for the synthesis of hybrid systems, have been synthesized from ketosteroid precursors. 3-Chloro-2-formyl-17,17-dimethyl-18-nor-5α-androstane-2,13-diene, (I), and methyl 3-chloro-4-formyl-12-oxo-5β-cholan-3-ene-24-oate, CHClO, (IV), have been synthesized using Vilsmeier reactions with 17β-hydroxy-17α-methyl-5α-androstan-3-one and methyl 3,13-dioxo-5β-cholan-24-oate, respectively. These products have been fully characterized using IR spectroscopy, H and C NMR spectroscopy, and high-resolution mass spectrometry, and in the case of (IV), a single-crystal X-ray diffraction study. Crystal structures have also been determined for the known analogues 3-chloro-2-formyl-17-oxo-5α-androst-2-ene, CHClO, (II), 3-chloro-2-formyl-5α-cholest-2-ene, CHClO, (III), and the absolute and relative configurations are assigned for all four compounds (I)-(IV): when the fusion between rings A and B is trans, 3-chloro-2-formyl products are formed, but when this ring fusion is cis, a 3-chloro-4-formyl product results. The formation of (I) involves not only chloroformylation at ring A, but also dehydration and the 1,2 migration of a methyl group at ring D. In each of (II), (III) and (IV), rings B and C adopt almost perfect chair conformations, while ring A adopts a half-chair conformation. Ring D adopts an envelope conformation in each of (II) and (III), albeit differently folded in the two compounds, while in (IV), it adopts a half-chair conformation. A single C-H...O hydrogen bond links the molecules of (II) into C(6) chains which are linked into sheets by means of carbonyl-carbonyl interactions. The molecules of (IV) are linked into simple C(7) chains, again by a single C-H...O hydrogen bond, but there are no direction-specific interactions in (III) that are structurally significant.
两种在A环中同时含有氯和甲酰基取代基、用作合成杂化体系前体的新型功能化甾体，已由酮甾体前体合成。3-氯-2-甲酰基-17,17-二甲基-18-降-5α-雄甾烷-2,13-二烯（I）和3-氯-4-甲酰基-12-氧代-5β-胆烷-3-烯-24-酸甲酯（CHClO，IV），分别通过与17β-羟基-17α-甲基-5α-雄甾烷-3-酮和3,13-二氧代-5β-胆烷-24-酸甲酯的Vilsmeier反应合成。这些产物已通过红外光谱、氢和碳核磁共振光谱以及高分辨率质谱进行了全面表征，对于（IV），还进行了单晶X射线衍射研究。还测定了已知类似物3-氯-2-甲酰基-17-氧代-5α-雄甾-2-烯（CHClO，II）、3-氯-2-甲酰基-5α-胆甾-2-烯（CHClO，III）的晶体结构，并为所有四种化合物（I）-（IV）指定了绝对和相对构型：当A环和B环之间的稠合为反式时，形成3-氯-2-甲酰基产物，但当这种环稠合为顺式时，得到3-氯-4-甲酰基产物。（I）的形成不仅涉及A环的氯甲酰化，还涉及脱水以及D环上甲基的1,2迁移。在（II）、（III）和（IV）中的每一个中，B环和C环几乎呈完美的椅式构象，而A环呈半椅式构象。在（II）和（III）中的每一个中，D环呈信封式构象，尽管在这两种化合物中折叠方式不同，而在（IV）中，它呈半椅式构象。一个单C-H...O氢键将（II）的分子连接成C(6)链，这些链通过羰基-羰基相互作用连接成片。（IV）的分子同样通过一个单C-H...O氢键连接成简单的C(7)链，但在（III）中没有具有结构意义的方向特异性相互作用。
