Solenopsin synthesis

Improved synthesis by this method has been achieved in order to obtain solenopsin A (Id) more stereoselectively 388). A cis and trans mixture of pyridine derivative 158, obtained from 156 by the Wittig reaction, was reduced by Raney nickel catalyst in the presence of PtOj to yield the m-piperidine (Ic). The Af-nitroso derivative 159, obtained from Ic by treatment with isoamyl nitrite, was treated with potassium rert-butoxide and then subjected to hydrogenolysis over Raney nickel to give a mixture of ( )-solenopsin A (Id, 1 part) and its isomer (Ic, 1 part) (Scheme 3). 

In addition, stereoselective synthesis of solenopsin A has been reported by four research groups. An approach utilizing the stereoselective reductive de-cyanation (596) starts with aminonitrile 229, prepared from 2-picoline. It was selectively hydrogenated in the presence of Pd-C, followed by alkylation with undecyl bromide, affording 231. Reductive decyanation of 231 with NaBH4 in MeOH led to predominant (8 2) formation of the trans isomer (232) which was then debenzylated to ( )-solenopsin A (Id). The cis product (Ic) was in turn prepared by treatment of 231 with sodium in liquid ammonia followed by de-benzylation (Scheme 10). 

Cycloaddition reaction of the l-acyl-l,2-dihydropyridine derivative 240 with methyl cyanodithioformate afforded adduct 241, which was converted by three steps to solenopsin A (Id) (Scheme 13) (399). This route constitutes a completely stereoselective synthesis of this alkaloid however, details are not available. 

As shown in Table I, this reaction sequence has wide generality and is readily applicable to the straightforward synthesis of various naturally occurring alkaloids such as coniine,9 pumiliotoxin C,11 1 and solenopsin A and B.11 Oxime sulfonates of either linear or cyclic structures may be used. Obviously, the regioselectivity of the reaction follows the general rule of... 

A synthesis of arecoline (17) from acetaldehyde has been described.17 Sederine (18) is a minor base occurring in Sedum acre-, its structure has been settled by spectral and chemical study, but its stereochemistry has yet to be established.18 A new total synthesis of racemic solenopsin A (19) (fire-ant venom) has been published the pathway is outlined in Scheme 2.19... 

A variety of alkaloids bind to or intercalate with DNA or DNA/RNA processing enzymes and affect either transcription or replication (quinine, harmane alkaloids, melinone, berberine), act at the level of DNA and RNA polymerases (vinblastine, coralyne, avicine), inhibit protein synthesis (sparteine, tubulosine, vincrastine, lupanine), attack electron chains (pseudane, capsaicin, solenopsine), disrupt biomembranes and transport processes (berbamine, ellipticine, tetrandrine), and inhibit ion channels and pumps (nitidine, caffeine, saxitoxin). In addition, these natural products attack a variety of other systems that can result in serious biochemical destabilization... 

Electron chains. The respiratory chain and ATP synthesis in mitochondria demand the controlled flux of electrons. This target seems to be attacked by ellipticine, pseudane, pseudene, alpinigenine, sanguinarine, tetrahydropalmatine, CH3-(CH2)i4-2,6-methyl-piperidines, capsaicin, the hydroxamic acid DIMBOA, and solenopsine. As mentioned before, however, only a few alkaloids have been evaluated in this context (Table V). 

Treatment of a wide variety of oxime sulfonates with several equivalents of alkyl-aluminum reagents in CH2CI2 resulted in formation of the imines, which were directly reduced with excess DIBAH to give the corresponding amines, as shown in Sch. 19. This organoaluminum-promoted Beckmann Rearrangement of oxime sulfonates has been successfully applied to the stereoselective synthesis of naturally occurring alkaloids, pumiliotoxin C, and solenopsin A and B, as illustrated in Sch. 20 [43]. 

Diketones and their aldol-derived cyclohexenones are obtained from alkylation of l-benzyl-2,6-di-cyanopiperidine followed by hydrolysis. - This dicyano analog of (47) provides a new method for the synthesis of rra/u-2-mediyl-6-ui ecylpiperidine (solenopsin), a-propylpiperidine (coniine) and other 2,6- alkylpiperidine alkaloid. 

The isolable imine (39), which is obtainable by the rearrangement of 2-undecylcyclopentanone oxime mesylate with MesAl, can be transformed to either the cis or trans isomer with high stereoselectivity depending on the choice of the reducing agents (Scheme 3). Reduction of (39) with MesAl-LiAlHt completes a short synthesis of solenopsin A (40). ... 

C=NOH CHNHi, Oximes are reduced selectively to amines in the presence of carbon-carbon double bonds by NaBH4 and M0O3. NaBH4 and NiCl2 6H20 effect reduction of both groups in 90-95% yield. This reduction was used in the final steps in a synthesis of solenopsin A (1), a constituent of fire ant venom (equation I). 

A number of groups have reported syntheses of various ant toxins see, for example, Y. Moriyama et al., Tetrahedron Letters, 1977, 825 R.K. Hill and T. Yuri, Tetrahedron, 1977, 33, 1559). A total synthesis of solenopsin-A is illustrative (K. Fuji, K. Ichikawa and E. Fujita, Chem.pharm. Bull., 1979, 27, 3183) (Scheme 5). 

At atmospheric pressure, the conversion of sterically hindered primary and secondary alcohols into the corresponding phenyl sulfide derivatives with a BusP-PhSSPh system occurs in low yields (0-56%) at 1.0 GPa pressure, the same reactions have given a 65-100% yield.Thus, this reaction has been used in the seven-step enantioselective synthesis of (-)-solenopsin... 

Reaction of A -alkoxycarbonylpyridinium salts with Qrignard reagents has been used in synthesis of natural products Lupinine (92) (93JOC(58)7732), Solenopsin A (93) (94TL(35)829), and 2,3-dihydro-4-pyridones (94TL(35)3927>. 

Scheme 11 Synthesis of ( )-solenopsin A via Ru-catalyzed directed C-H alkylation...

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