Attempts to convert 3β‐acetoxy‐5,19‐cyclo‐pregna‐6,20‐dione (8) into a cyclocitrinol‐related steroid with a bicyclo[4.4.1]‐undecane AB‐ring substructure through a Lewis acid‐assisted fragmentation failed. Instead, treating 8 with an excess of Ac2O and BF3·Et2O afforded B‐homo steroid 9 in 90 % yield. This unexpected rearrangement is assumed to proceed via an intermediate bicyclobutonium cation. Remarkably, tricyclo[4.4.1.0]undecane‐1‐one (rac‐13), prepared as a model substrate, did not react under the same conditions. However, by screening various Lewis acids, stannous triflate was identified as a particularly efficient reagent for this and related Lewis acid‐assisted ring‐opening reactions of cyclopropyl ketones in the presence of Ac2O, and even catalytic amounts of Sn(OTf)2 (5 mol‐%) proved to be effective.

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The BF3·Et2O-promoted reaction of 3β-acetoxy-5,19-cyclo-pregnan-6β-ol-20-one with different nucleophiles was investigated. B-homo steroids (3β-acetoxy-B-homo-6a-β-alkoxy-pregna-5(10)-en-20-ones) were obtained with primary and secondary alcohols, while the reaction with common carboxylic acids selectively afforded the corresponding 3β-acetoxy-6β-(acyloxymethyl)-pregna-5(10)-en-20-ones. The transformations are supposed to proceed via the rearrangement of a cyclopropyl-methyl cation (bicyclobutonium) intermediate, which is regioselectively opened in dependence on the nucleophile employed. The method represents an efficient, diversity-oriented entry to new B-ring-modified steroids, which are of potential pharmaceutical relevance.

A synthetic approach towards (5R)‐5‐methyl‐6‐oxa‐desacetamido colchicine as a conformationally defined non‐natural colchicine analog with a modified B‐ring was undertaken. The synthetic strategy was based on a Rh‐catalyzed cascade reaction involving a [5+2] cycloaddition of a carbonyl ylide intermediate as a key step, in which both seven‐membered rings of the polycyclic framework are formed in a single operation. Starting from 2‐iodo‐3,4,5‐trimethoxy‐acetophenone, an upper side‐chain was constructed through enantioselective CBS reduction (up to 75 % ee) and propargylation, while a lower succinoyl side‐chain was attached either throughiodine–magnesium–copper exchange and subsequent reaction with methyl 4‐chloro‐4‐oxobutanoate, or by Pd‐catalyzed Stille cross‐coupling with 2‐tributylstannyl‐5‐methoxyfuran followed by hydrolytic furan‐opening. Treatment of an α‐diazoketone intermediate with Rh2(OAc)4 (3 mol‐%)initiated the diastereoselective key cyclization cascade (≥97:3 dr). Treatment of the cycloadduct 3 with Et2AlCl afforded an interesting 11,12‐dihydrocolchicine analog 24, which, however, could not be oxidized to the corresponding tropolone. Structural assignments were confirmed by X‐ray crystallography. While compounds 3 and 24 did not exhibit noteworthy cytotoxic activity by themselves, they were found to strongly enhance the cytostatic (apoptosis‐inducing) activity of doxorubicin against resistant Nalm‐6 cells (i.e., in a synergy effect).

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