Pancratistatin is a phenanthridone-type natural product isolated from several plants of the Amaryllidaceae family. Its potent antiproliferative, antivascular, antiviral, and antiparasitic properties have attracted the attention of synthetic, biological, and medicinal chemists. Pancratistatin’s low natural availability and complex structure have steered many of these research projects toward the preparation of its simplified synthetic analogues with useful levels of activity. In this work we have developed synthetic chemistry aimed at the preparation of pancratistatin analogues with a truncated cyclitol portion of the molecule. The described synthetic pathways are based on a highly anti-diastereoselective arylcuprate conjugate addition to γ-alkoxy-α,β-enoates and syn-selective azidation at the α-position of ester enolates. Analogues with the formally cleaved C3−C4 bond, and thus containing an open ring C, as well as a compound containing a truncated lactol moiety in lieu of the cyclitol, were prepared. Several of the analogues exhibited weak antiproliferative activity, with the highest potency observed in the case of the lactol analogue. From these results implications for the design of future pancratistatin analogues are discussed. Furthermore, the synthetic pathways can be used to construct pancratistatin-mimetic libraries, in which the cyclitol moiety is replaced by other cyclic motifs.

Synthesis of Structurally Simplified Analogues of Pancratistatin: Truncation of the Cyclitol Ring / Madhuri, Manpadi; A. S., Kireev; I. V., Magedov; J., Altig; P., Tongwa; Antipin, M. Y. u.; Evidente, Antonio; W. A. L., van Otterlo; A., Kornienko. - In: JOURNAL OF ORGANIC CHEMISTRY. - ISSN 0022-3263. - STAMPA. - 74:18(2009), pp. 7122-7131. [10.1021/jo901494r]

Synthesis of Structurally Simplified Analogues of Pancratistatin: Truncation of the Cyclitol Ring

EVIDENTE, ANTONIO;
2009

Abstract

Pancratistatin is a phenanthridone-type natural product isolated from several plants of the Amaryllidaceae family. Its potent antiproliferative, antivascular, antiviral, and antiparasitic properties have attracted the attention of synthetic, biological, and medicinal chemists. Pancratistatin’s low natural availability and complex structure have steered many of these research projects toward the preparation of its simplified synthetic analogues with useful levels of activity. In this work we have developed synthetic chemistry aimed at the preparation of pancratistatin analogues with a truncated cyclitol portion of the molecule. The described synthetic pathways are based on a highly anti-diastereoselective arylcuprate conjugate addition to γ-alkoxy-α,β-enoates and syn-selective azidation at the α-position of ester enolates. Analogues with the formally cleaved C3−C4 bond, and thus containing an open ring C, as well as a compound containing a truncated lactol moiety in lieu of the cyclitol, were prepared. Several of the analogues exhibited weak antiproliferative activity, with the highest potency observed in the case of the lactol analogue. From these results implications for the design of future pancratistatin analogues are discussed. Furthermore, the synthetic pathways can be used to construct pancratistatin-mimetic libraries, in which the cyclitol moiety is replaced by other cyclic motifs.
2009
Synthesis of Structurally Simplified Analogues of Pancratistatin: Truncation of the Cyclitol Ring / Madhuri, Manpadi; A. S., Kireev; I. V., Magedov; J., Altig; P., Tongwa; Antipin, M. Y. u.; Evidente, Antonio; W. A. L., van Otterlo; A., Kornienko. - In: JOURNAL OF ORGANIC CHEMISTRY. - ISSN 0022-3263. - STAMPA. - 74:18(2009), pp. 7122-7131. [10.1021/jo901494r]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/363915
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact