Studies aiming the synthesis of the indolizidine alkaloids (+)-Ipalbidine and (+)-Antofine

Studies aiming the synthesis of the indolizidine alkaloids (+)-Ipalbidine and (+)-Antofine

Bertonha, Ariane F.; Burtoloso*, Antonio C. B.

Abstract:

The indolizidine skeleton is present in a large number of compounds with interesting biological profiles. The (+)-ipalbidine 1 and (+)-antofine 2 have, among others, analgesic and anticancer properties, respectively. However, there are few short, divergent and enantioselective syntheses for these compounds. This work presents a new route to obtain the indolizidine skeleton present in these alkaloids, employing a cyclization reaction from α- chloroketones (R1 = CH3 (+)-Ipalbidine, R2 = Ar, Phenanthroindolizidines), which can be easily prepared from (S)-prolinal (Scheme 1). The key steps of this strategy are: an olefination reaction (Wittig or Horner-Wadsworth-Emmons); the preparation of α-chloroketones; and converting them into the indolizidine skeleton.

The indolizidine skeleton is present in a large number of compounds with interesting biological profiles. The (+)-ipalbidine 1 and (+)-antofine 2 have, among others, analgesic and anticancer properties, respectively. However, there are few short, divergent and enantioselective syntheses for these compounds. This work presents a new route to obtain the indolizidine skeleton present in these alkaloids, employing a cyclization reaction from α- chloroketones (R1 = CH3 (+)-Ipalbidine, R2 = Ar, Phenanthroindolizidines), which can be easily prepared from (S)-prolinal (Scheme 1). The key steps of this strategy are: an olefination reaction (Wittig or Horner-Wadsworth-Emmons); the preparation of α-chloroketones; and converting them into the indolizidine skeleton.

Palavras-chave:

DOI: 10.5151/chempro-15bmos-BMOS2013_201391415130

Referências bibliográficas

• [1] 1 Prado, V. S. Estudos visando a síntese do alcaloide indolizidínico (+)- ipalbidina. Thesis (Master) – Universidade de São Paulo, Instituto de Química de São Carlos, São Carlos, 2012.
• [2] 2 Bøgesesø, K. P.; Arnt, J.; Lundmark, M. e Sundell, S. J. Med. Chem. 1987, 30, 142-150.

Como citar:

Bertonha, Ariane F.; Burtoloso*, Antonio C. B.; "Studies aiming the synthesis of the indolizidine alkaloids (+)-Ipalbidine and (+)-Antofine", p-78-78. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-BMOS2013_201391415130