This review is focused on recent synthetic achievements and ongoing work in our laboratory using phenylglycinol-derived oxazolopiperidone lactams as starting materials for the enantioselective synthesis of piperidine-containing alkaloids: madangamines, 2,5-disubstituted decahydroquinoline and 1-substituted tetrahydroisoquinoline alkaloids, the indole alkaloids 20S- and 20R-dihydrocleavamine and quebrachamine, and indole alkaloids of the uleine and silicine groups.
For alternative procedures, see: (a) RoyerJ., HussonH.P. (1993) A new potential acyl iminium ion for the asymmetric synthesis of piperidine derivatives. Heterocycles, 1493–1496; (b) Terán JL, Gnecco D, Galindo A, Juárez J, Bernès S, Enríquez RG. (2001) New methodology for the synthesis of enantiopure (3R,2aR)-(–)-3-phenylhexahydrooxazolo[3,2-a]pyridin-5-one: a synthesis of (S)-(+)-coniine. Tetrahedron: Asymmetry, 12, 357–360; (c) Airiau E, Spangenberg T, Girard N, Schoenfelder A, Salvadori J, Taddei M, Mann A. (2008) A general approach to aza-heterocycles by means of domino sequences driven by hydroformylation. Chemistry, A European Journal, 14, 10938–10948; (d) Tojino M, Otsuka N, Fukuyama T, Matsubara H, Ryu I. (2006) Selective 6-endo cyclization of the acyl radicals onto the nitrogen of imine and oxazoline C-N bonds Journal of American Chemistry Society, 128, 7712–7713.
2.
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EscolanoC., AmatM., BoschJ. (2006) Chiral oxazolopiperidone lactams: versatile intermediates for the enantioselective synthesis of piperidine-containing natural products. Chemistry, A European Journal, 12, 8198–8207.
5.
(a) KongF., AndersenR.J., AllenT.M. (1994) Madangamine A, a novel cytotoxic alkaloid from the marine sponge Xestospongia ingens. Journal of the American Chemical Society, 116, 6007–6008;(b) Kong F, Graziani EI, Andersen RJ. (1998) Madangamines B-E, pentacyclic alkaloids from the marine sponge Xestospongia ingens. Journal of Natural Products, 61, 267–271; (c) De Oliveira JHHL, Nascimento AM, Kossuga MH, Cavalcanti BC, Pessoa CO, Moraes MO, Macedo ML, Ferreira AG, Hajdu E, Pinheiro US, Berlinck RGS. (2007) Cytotoxic alkylpiperidine alkaloids from the brazilian marine sponge Pachychalina alcaloidifera. Journal of Natural Products, 70, 538–543.
6.
(a) AmatM., PérezM., MinagliaA.T., CasamitjanaN., BoschJ. (2005) An enantioselective entry to cis-perhydroisoquinolines. Organic Letters, 7, 3653–3656;(b) Amat M, Pérez M, Proto S, Gatti T, Bosch J. (2010) First enantioselective synthesis of the diazatricyclic core of madangamine alkaloids. Chemistry, A European Journal, 16, 9438–9441.
7.
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8.
AmatM., PérezM., GrieraR., ProtoS., FabregatR., BoschJ. (2010) An enantiomeric scaffolding strategy for the synthesis of alkaloids: Use of chiral oxazolopiperidone lactams. 3rd EuCheMS Chemistry Congress, Nürnberg, Germany.
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12.
(a) AmatM., GrieraR., FabregatR., MolinsE., BoschJ. (2008) A biomimetic enantioselective approach to the decahydroquinoline class of dendrobatid alkaloids. Angewandte Chemie International Edition, 47, 3348–3351;(b) Amat M, Fabregat R, Griera R, Florindo P, Molins E, Bosch J. (2010) Biomimetic construction of the hydroquinoline ring system. Diastereodivergent enantioselective synthesis of 2,5-disubstituted cis-decahydroquinolines. The Journal of Organic Chemistry, 75, 3797–3805.
13.
AmatM., FabregatR., GrieraR., BoschJ. (2009) A general synthetic route to enantiopure 5-substituted cis-decahydroquinolines. The Journal of Organic Chemistry, 74, 1794–1797.
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(a) SaxonJ.E. (1983) The aspidospermine group. In Indoles. The Monoterpenoid Indole Alkaloids. Vol. 25, SaxtonJE. (Ed). In The Chemistry of Heterocyclic Compounds; Weissberger A, Taylor EC. (Eds). Wiley, New York, part 4, 331–465; (b) Saxon JE. (1994) The aspidospermine group. In Indoles. The Monoterpenoid Indole Alkaloids. Vol. 25, Saxton JE. (Ed). In The Chemistry of Heterocyclic Compounds; Weissberger A, Taylor E.C. (Eds). Wiley, Chichester, Suppl. to part 4, 357-436.
16.
(a) AmatM., EscolanoC., LozanoO., LlorN., BoschJ. (2003) Enantioselective synthesis of cis- and trans-3,5-disubstituted piperidines. Synthesis of 20S- and 20R-dihydrocleavamine. Organic Letters, 5, 3139–3142;(b) Amat M, Escolano C, Lozano O, Gómez-Esqué A, Griera R, Molins E, Bosch J. (2006) Alkylation of phenylglycinol-derived oxazolopiperidone lactams. Enantioselective synthesis of β-substituted piperidines. The Journal of Organic Chemistry, 71, 3804-2815.
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19.
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20.
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