Solamin, total synthesis

The acetogenin (+)-solamin and analogs were prepared via a ruthenium-catalyzed Alder-ene reaction/butenolide formation (Scheme 37).96 Of particular note is the ability of the ruthenium to catalyze the reaction in the presence of free hydroxyls, sulfides, and sulfones. Yields ranged from 65% for the sulfide to 88% for the sulfone. Trost has also applied this reaction to the total synthesis of (+)-ancepsenolide, which features a bis-Alder-ene reaction (Scheme 38).97... 

One of the earliest and most important discoveries in metal-catalyzed asymmetric synthesis is Sharpless s Ti-catalyzed epoxidation of allylic alcohols. A mere mention of all the total syntheses that have used this technology would require a separate review article Here, we select Trost s masterful total synthesis of solamin (100, Scheme 14), for its beautiful and multiple use of Sharpless s asymmetric epoxidation.1161 Optically pure epoxy alcohol 95 is converted to both epoxy iodide 96 and diol 97 The latter two intermediates are then united to give 98, which is oxidized and converted to dihydrofuran 99 by a Ramberg-Backlund transformation. The Re catalyzed butenolide annulation that is used to afford the requisite unsaturated lactone only adds to the efficiency of this beautiful total synthesis. 

Scheme 14. Trost s use of directed asymmetric epoxi-dation in the enantioselect-ive total synthesis of solamin (1994).

As part of the total synthesis of the triterpene (+)-a-onocerin, one of the first total syntheses in which RuO played a key role, a diphenylethyleneacetoxyketone was oxidised to the corresponding acetoxyketoacid by RuO /aq. Na(10yacetone. Aromatic ring oxidation was also involved (cf. 3.3.1 below) [219]. An oxidative cyclisation of a 1,5-diene to a diol by RuCl3/Na(10 )/wet SiO /THF formed part of the synthesis of the antitumour agent cw-solamin [220]. 

An asymmetric permanganate-promoted oxidative cyclization of 1,5-dienes using a chiral phase-transfer catalyst was recorded <2001AGE4496>, and a diastereoselective permanganate-mediated oxidative cyclization with an Oppolzer sultam has been employed in the total synthesis of m-solamin <20020L3715>. In a metal-oxo-mediated approach to the synthesis of 21,22-di- /)7-membrarollin based on the use of a camphor-derived Oppolzer sultam as... 

Total synthesis of solamin and reticulatacin, two mono-THF acetogenins, confirms their absolute configuration. 

Further efforts by several groups have resulted in total syntheses of muricatacin 38,6, 42-44 (-)-bullatacin (41) (the enantiomer of the natural product), solamin 42, and reticulatacin 24, (Figure 22). All of the above have been synthesized by methods that establish unambiguously their absolute configuration. All of the stereochemical information obtained so far by total synthesis is in complete agreement with the conclusions reached earlier by the methods described in this chapter. 

Scheme 50 Asymmetric furan cyclization and the formal total synthesis of (+)-cw-solamin by...

---