Cyclopropyl steroids

Spiro-pyrazoline derivatives (18) are obtained smoothly from 16-methy-lene-17-ketones (17). ° The sole products formed from (18) by pyrolysis or cleavage in the presence of boron trifluoride etherate, are the 16-spiro-cyclopropyl steroids (19). ... 

Cyclopropanation of steroids (363) at the 1,2-position with malonate in the presence of potassium t-butoxide and tetramethylguanidine takes place with formation of the di(alkoxycarbonyl)cyclopropane derivatives (364) accompanied by steroidal cyano-alkoxycarbonylcyclopropanes (365). When the reaction is carried without tetramethylguanidine only minor amounts of cyclopropyl steroids are isolated The formation of the cyano compound is explained by an initial nucleophilic displacement of bromine by the tetramethylguanidine moiety, followed by several steps (equation 119). Although the reaction of equation 120 cannot be classified as a MIRC reaction sensu strictu the formation of cyclopropa[c]cinnolines (367) via an intramolecular 1,1-cycloaddition of nitrilimines is mentioned here. Treatment of o-vinylphenyl-substituted chloroglyoxylate... 

The synthesis of the steroidal 2a,3a-cyclopropanol (137b) has been described. The 3-bis-(2-chloroethoxy)-derivative (135) was pyrolysed in vacuo to give the olefin (136). This with excess Simmons-Smith reagent gave the cyclopropyl steroid (137a), which with butyl-lithium liberated the free cyclopropanol (137b) this was converted into 17j8-hydroxy-2a-methyl-5a-androstan-3-one (138) by base. 

An interesting study reports carbene additions to the androstane enol ether (139). Addition of dibromo- and dichloro-carbene gave the D-homo-a-halo-genoenones (140a) and (140b), respectively. The Simmons-Smith reaction on (139) afforded the l6a,17a-cyclopropyl steroid (141). Whereas treatment of (141) with acid provided the D-homo-derivative (142), reaction with iodine, followed by... 

The most frequently encountered examples of cyclopropyl ring opening reactions in the steroid field are usually associated with angular or side chain methylation sequences. In fact, isotope labeling of the C-19 angular methyl group is the only reported application of this reaction for deuteration or tritiation pui poses. 

The first substance examined in the steroid field was 3j6-hydroxycholest-4-ene (1) and the epimeric 3a-alcohol (3). These compounds react stereospecifically in dry ether with the Simmons-Smith reagent to yield the isomeric cyclopropyl carbinols (2) and (4) in 90 % and 67 % yields, respectively. The rate of this reaction is about one fifth of that observed with simple cyclic car-binols. ... 

For a convenient photochemical preparation of steroidal a-cyclopropyl ketones from the A -pyrazoline derivatives of the corresponding a, -unsaturated ketones, cf. ref. 50. 

Shoppee, C. W. Steroids and the Walden Inversion. Part II. Derivatives of d5-Cholestene and zl5-Androstene. J. chem. Soc. [London] 1946, 1147. 203- Siegel, S., and C. G. Bergstrom The Effect of a Cyclopropyl Group on a Displacement Reaction at an Adjacent Saturated Carbon Atom. I. The Ethanolysis of Cyclopropylmethyl Benzenesulfonate. J. Amer. chem. Soc. 74, 145 (1952). 

Intermolecular cyclopropanation of diazoketones is an effective method in organic synthesis. Wenkert and coworkers have applied this methodology to the synthesis of a substantial number of cyclopropane adducts 2868, 2969 and 307° which are synthetic intermediates in the preparation of natural products (equations 41—43). Copper catalysts were chosen for these transformations. Another interesting application of intermolecular cyclopropanation is to be found in Daniewski s total synthesis of an aromatic steroid. Palladium(II) acetate catalysed decomposition of 4-bromo-l-diazo-2-butanone in the presence of m-methoxystyrene was used to give the cyclopropyl ketone 31 which was a key intermediate in the total synthesis (equation 44)71. 

Palladium diacetate catalyses the reaction of diazomethane with a(3-unsaturated ketones to give cyclopropyl ketones in high yields. Steroidal examples include formation of the products (89) and (90) from the corresponding enones.106... 

Steroids containing cyclopropyl groups in the side chain, as exemplified by gorgosterol (17) from the gorgonia Plexaura flexnosa as well as the zoanthid Palythoa sp. . 

This initial survey of naturally occurring cyclopropanoid metabolites raises several questions relating to the biochemistry including function and metabolism of the compounds and in particular the cyclopropyl group. In the bulk of this chapter we summarize what evidence is available on modes of biosynthesis and degradation of cyclopropyl substituents. While in several cases, e.g. in terpenoids and steroids of the cycloartenol (20) case, biogenetic tracer studies or stereochemical probes have been carried out and are quite revealing about precursor-product relationships, there are very few cases indeed where specific enzymatic catalysts have been identified, isolated, and characterized for action on specific cyclopropane substrates. 

The scheme for steroid biosynthesis is the same in both plants and animals up to the formation of the carbocation 3-2. The biosynthesis diverges at this point in animals the methyl group at Cg migrates to afford lanosterol (4-1) as an isolable product (Scheme 2.4). The first steroidal product that can be isolated in plants, cycloartenol (4-2), features a cyclopropyl ring fused on to ring B at carbons 9,10. 

Pattenden also proposed a novel type of cascade for the steroid skeleton construction [39]. Starting from the relatively elaborated precursor 78, that notably bears a cyclopropyl ring, a double 6-endo-trig creates cw-hydrindane 80 (Scheme... 

An ingenious synthesis of steroidal annulenes has appeared. The close relationship of annulenes to the classical aromatic substance naphthalene stimulated the synthesis of l,6-methano-[10]annuleno-steroids, which are analogues of equilenin (97). The y,5-cyclopropyl-a -unsaturated ketone (98) was the initial target. Treatment of the cyclopropyl ketone (98) with acetic anhydride and methyl orthoformate in the presence of an acid catalyst then gave (99). Conversion of the cycloheptatriene (99) into the requisite 10 c-electron system (100) was then accomplished by dehydrogenation. ... 

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