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The work concerns the reactivity of 17β-hydroxy-17α-substituted androstanes 1-9. Depending on the nature of the 17α-substituent, the presence of the neighboring 16-oximino group, and the reagent used, these compounds can undergo retroaddition (10-12) and fragmentation-cyclization (14-16) reactions.

Starting from 3β-acetoxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile (1), 3β-acetoxy-16,17-secoandrost-5-ene-16-nitrile (4) was synthesized by a three-stage procedure. First, the formyl group of compound 1 was reduced, to yield the alcohol 2. Compound 2 was further transformed to the mesyloxy derivative 3, whose reduction with NaBH3CN gave compound 4. Apart from compound 4 as the main reaction product, two additional products were obtained, for which the GC/MS analysis suggested that they are 8(14) and 14 derivatives of compound 4. Compound 4 was transformed into 3β-hydroxy-16,17-sesoandrost-5-ene-16-nitrile (7), the Oppenauer oxidation of which afforded 3-oxo-16,17-secoandrost-4-ene-16-nitrile (8).

Starting from methyl salicylate and 2-amino-2-(hydroxymethyl)propane-1,3-diol 1a, or 2-amino- 2-methylpropane-1-ol 1b, the 2-oxazoline derivatives 2a, 2b or 3, as well as mono- 4a and 4b and bis- 5a and 5b derivatives of salicylic acid were synthesized. Reactions were performed by microwave irradiation in the presence of tetrabutylammonium bromide or metallic sodium as catalyst, as well as by conventional heating. Microwave-induced reaction of some diols, diamines and amino alcohols with methyl salicylate gave mono- and/or bis- derivatives of salicylic acid 4c, 5c, 5d, 6c, 8c, 7a, 7b, 8a and 8b. The mono- and bis-salicyloyl derivatives 4c, 5c and 5d were transformed to the corresponding phenyl-azo derivatives 9, 10c and 10d. The structure of compound 3 was proved by the X-ray analysis and the R-configuration on its stereocenter was confirmed. The antioxidant and cytotoxic activities of the synthesized derivatives were evaluated in a series of in vitro tests. Compounds 5d, 8b and 8c exhibited very strong activity against hydroxyl radical. Six 4c, 5d, 8a-c, 10c of 16 tested compounds inhibited growth of MDA-MB-231 cells at a nanomolar concentration. Compounds 8c and 10c showed high cytotoxicity against MCF7 cells, whereas compounds 4c, 5d, 8a-c and 10d showed high activity against K562 cells. [ABSTRACT FROM AUTHOR]