Torgov synthesis

Because of its flexibility, the Torgov synthesis (see Scheme 6) is still used quite frequently for the preparation of modified steroids. Acid cyclization of 3-methoxy-8,14-seco-oestra-l,3,5(10),9(1 l)-tetraene-14,17-dione (96) gave a mixture of the A -bisdehydro-oestrone (97) and A -dehydro-14/8-hydroxy-8a-oestrone (98). Catalytic hydrogenation of (98) afforded 3-methoxy-14 -hydroxy-8a,9)8-oestrone (99a) and 79% of 3-methoxy-14)S-hydroxy-8a,9a-oes-trone (99b). Treatment of (99b) with thionyl chloride in pyridine provided, after hydrolysis, 59% of 3-methoxy-A -dehydro-8a-oestrone (100), which on hydrogenation yielded the 8a,14)S-oestrone analogue (101). 

CarbocycUc Steroids.— The Torgov synthesis continues to exhibit its great versatility and was recently employed in the first synthesis of B-homo-oestrone. Condensation of the vinyl alcohol (407) and 2-methy 1-cyclopentane-l,3-dione in the presence of l,4-diazabicyclo[2,2 ]octane and cyclisation with toluene-p-sulphonic acid gave the B-homo-oestrapentaene (409) in 33 % overall yield from 3-methoxybenzosuberone. A three-stage reduction by sodium borohydride, catalytic hydrogenation, and lithium-ammonia afforded 3-methoxy-B-homo-... 

The relative simplicity of the structure of estranes compared with those of other classes of steroids has made this structural class an attractive target for work aimed at total synthesis from so-called coal tar starting materials. About half a dozen syntheses have been developed, one of which, the Smith-Torgov synthesis, is probably stiU used commercially. 

Finally (d + aV dditions of 1-alkenyl and 1-alkynyl anions to carbonyl groups should be mentioned. Examples are the addition of vinylmagnesium bromide to ketones e.g. in the first step of Torgov s steroid synthesis (I.N. Nazarov, 1957), and the famous alkynylation of... 

During the course of a mass spectrometric study of D-homo-14-hydroxy steroids, it was necessary to prepare the corresponding C-8 deuterium labeled analogs. The preparation of these uncommon steroid derivatives has been achieved by repeating the Torgov total synthesis [(257) (262)] with a deuterium-labeled bicyclic starting material (258). Both of the resulting 14-hydroxy epimers, (261) and (262), exhibited better than 90% isotopic purity. ... 

In the first of these sequences, often called the Torgov-Smith synthesis, the initial step consists in condensation of a 2-alkyl-cyclopentane-l,3-dione with the allyl alcohol obtained from 6-methoxy-l-tetralone and vinylmagnesium chloride. Although this reaction at first sight resembles a classic SN displacement, the reaction is actually carried out with only a trace of base. 

The scheme used to prepare the direct 8-aza-analogue 21 of estrone bears at least formal similarity to the Torgov-Smith steroid total synthesis sequence. Acylation of the phenethylamine 9 with acryloyl chloride gives amide 16. Michael addition of dimethylamine followed by Bischler-Napieralski cyclodehydration gives the dihydroisoquinoline, 17. 

Narang, S A, Wightman, R H 1973, in ApSimon J (ed), The Total Synthesis of Natural Products Vol I, p 279, Wiley New York London Naruta, Y, Ushida, S, Maruyama, K. 1979 Chem Lett 1979,919 Nazarov, I N, Torgov, I V, Verkholetova, G 1957, Dokl Akad Nauk SSSR 112, 1067 Nedelec L, Gasc T, Buoourt, R 1974, Tetrahedron 30, 3263 Nefkens, G H L 1960, Nature (London) 185, 309... 

Synthesis of f -D-(l,6) linked disaccharides of N-fatty acylated 2-amino-2-deoxy-D-glucose an approach to the lipid A component of the bacterial lipopolysaccharide. Carbohydr. Res., 88, C10-C13 Kochetkov, N.K., Dmitriev, B.A., Malysheva, N.N., Chernyak, A.Ya., Klimov, E.M., Bayramova, N.E., and Torgov, V.I. (1975). Synthesis of O-p-D-mannopyranosy l-( 1 - 0-0-ot -L-rhamnopyranosy l-( 1 -3)-D-galacto-pyranose, the trisaccharide repeating-unit of the O-specific polysaccharide from Salmonella anatum. Carbohydr. Res. 15, 283-290... 

N. K. Kochetkov, V. I. Torgov, N. N. Malysheva, and A. S. Shashkov, Synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Salmonella Strasbourg, Tetrahedron, 36 (1980) 1099—1105. 

It is instructive to follow the evolution of the strategic principles with an example of the total synthesis of estrone 128 (Scheme 3.33), as it can be regarded historically as one of the trial cases used to evaluate the effectiveness of various synthetic approaches.The first total synthesis of estrone, reported in 1948 by Anner and Mischner, involved 18 steps with an overall yield of 0.1 % (based on the starting material, m-bromoanisole). In 1958, Johnson s group accomplished the synthesis in 10 steps with a 4.2% yield based on 2-methoxytetralone 129. Finally, in 1965, Torgov and co-workers carried out a six-step synthesis, also based on 129, but in 25% yield. 

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