Solamines

Solamine, 4A,4 A-bis(dimethylamino)-dibutylamine and its A/-hexanoyl derivative solacaproine (Eig. 5.1) were discovered as constituents of the roots of Solarium betaceum Cav. sub nom. Cyphomandra betacea (Cav.) Sendt., tree tomato (Evans et al. 1972). Solamine and its urethane (carbamate) derivative solaurethine (Fig. 5.1) were identified in the roots of S. carolinense L horse nettle (Evans and Somanabandhu 1977). 

Addition. The root-wood of Duboisia leichhardtii was found to contain tetrameth-ylputrescine (A,A -tetramethyl-l,4-diaminobutane) (Griffin 1967). 

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Coronar-Homocent (Fides) wfm Coropar (Redel) wfm wfm Solamin (Ardeypharm) wfm (Angelini)-comb. wfm... 

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).

Several natural products and pharmaceuticals have been made in which a TPAP-catalysed oxidation of a primary alcohol to aldehyde step occurs, and these are listed in 2.1.3. They include agardhilactone, (-)-ceratopicanol, eleutherobin, (-)-eriolangin, (-)-eriolanin, okadaic acid, QS-21A p, cis- rapamycin, solamin and taxol syntheses. 

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]. 

From plants belonging to the family of Solanaceae, five alkaloids were isolated containing symmetrical homospermidine as the basic backbone solamine (159), solapalmitine (160), solapalmitenine (161), solacaproine (162), and solaurethine (163). The characteristic features of all the com-... 

Hydrogenation of the mixture followed by hydrolysis gave solamine (159) and a mixture of palmitic acid (80%) and stearic acid (20%). The alkaloid containing stearic acid was not investigated further. The structure of sola-mine was confirmed by direct comparison with the synthetic 4,4 -bis(di-methylamino)dibutylamine. Treatment of solamine (159) with palmitoyl chloride and ( )-hexadec-2-enoyl chloride produced solapalmitine (160) and solapalmitenine (161), respectively (118,119). 

Solamine (159) was found to be the principal component of Cyphoman-dra betacea. By treatment of solamine with n-hexanoyl chloride, the second component of the same plant was formed, which was also hydrolyzed to form -hexanoic acid and solamine (120). Solaurethine (163), an alkaloidal component of another plant in the Solanaceae, was obtained by treatment of solamine (159) with ethyl chloroformate (121). 

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... 

Scheme 10-16. Total s3mthesis of cij-solamin by Makebe et al. and Cecil and Brown.

SYNS ANTI-GERM 77 ANTISEPTOL BENZETHONIUM CHLORIDE BENZETONIUM CHLORIDE BENZTTX)IMETHYL-p-(l,1,3,3-TETRAMETHYLBUTYL)PHENOXYETHOXY-ETHYLAMMONIUM CHLORIDE BZT DIAPP DIISOBLfTYLPHENOXYETHOXYETHYLDIMETHYL BENZYL AMMONIUM CHLORIDE DISILYN HYAMINE HYAMINE 1622 NCI-C61494 p-tert-OCTYXPHENOXYETHOXYETHYLDIMETHYLBENZYL AMMONIUM CHLORIDE PHEMERIDE PHEMEROL CHLORIDE PHEMITHYN POLYMINE D QUATRACHLOR SOLAMINE... 

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. 

The four synthetic isomers of rir-solamin were indistinguishable from each other and from natural rir-solamin on the basis of their IR, MS, H-NMR, and 13C-NMR spectra, owing to the length and flexibility of the spacer connecting the tetrahydrofurandiol and butenolide moieties. Optical rotation values obtained for each of the pairs of diastereomers were also very similar, and consistent with the known fact that the contribution to optical rotation from the butenolide moiety dominates that from a pseudosymmetrical... 

Subsequently, Figadere and coworkers30 analyzed natural rir-solamin by enantioselective HPLC, and found it to be a 9 8 mixture of rir-solamin A (36) and cis-solamin B (37). Thus, natural ar-solamin was stereochemi-cally heterogeneous demonstrating that enantioselective chromatography is indeed a powerful technique in... 

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