Synthesis solamin

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. 

Roblot et al. (63) were the first to report the hemi-synthesis of a natural acetogenin of Annonaceae. They have shown that treatment of a natural precursor, diepomuricanin-A 121, by NaOH followed by acetylation with Ac20-pyridine afforded solamin diacetate 155 in 60 % yield. Unfortunately the composition of the expected diastereomeric mixture was not discussed. Indeed opening of the bis-epoxide system at either C-15 or C-20 would lead to two different compounds 155 and 156 with the same relative configuration but of opposite absolute configuration across the THF ring (Fig. 23). 

The second set of examples involves the use of thionium ions as electrophiles in inter- and intramolecular processes to obtain a-substituted sulfides (see 24 25, Scheme 20.7T which is the most common type of Pummerer reaction. Applications of this classical Pummerer rearrangement are exemplified in the synthesis of trans-solamin, the synthesis of indolizidine alkaloids, and the synthesis of the CDE ring of erinacine E. The first exanple fScheme 20.10 uses Pummerer chemistry in the generation of a thionium ion, which reacts in an intermolecular tin-mediated ene reaction the second one fScheme 20.11 uses Pummerer chemistry to introduce a nitrogen-containing heterocycle by intramolecular addition to form the coniceine core and the third example fScheme 20.12 is an intramolecular silicon-induced Pummerer reaction with oxygenated nucleophiles applied to the synthesis of a precursor of erinacine. Details of these Pummerer-based strategies are discussed below. 

The Lewis acid promoted (typically boron trifluoride) condensation of cyclic iminium ions with TMSOF provides a facile route to a variety of substituted butenolide products. In this manner, the Lewis acid promoted condensation of pyrrolidine derived iminium ions with TMSOF provides the desired threo-product as the major isomer (eq 26). This step is pivotal in the synthesis of a tachykinin NK-2 receptor antagonist, the C1-C32 fragment of aza-solamin and various biologically active indolizidinones. ... 

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

In addition to the (+)-c/s-solamin example outlined above, the Donohoe group has also applied their method in the synthesis of the annonaceous acetogenin (+)-sylvaticin (Scheme 51) [56], (for the application of the oxidative cyclization chemistry to bicyclic ring systems see [57]). Exposure of a mixture of tetradeca-tetraene isomers (commercially available as a mixture of three stereoisomers) or the pure , -isomer to AD-mix-a gave 191 in an 18 % yield after bis-acetonide... 

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