A new practical route to chaetomellic acid A (ACA), based on the copper catalysed radical cyclization (RC) of (Z)-3-(2,2-dichloropropanoyl)-2-pentadecylidene-1,3-thiazinane, is described. Remarkably, the process entailed: (i) a one-pot preparation of the intermediate N-a-perchloroacyl-2-(Z)-alkyliden-1,3-thiazinanes starting from N-(3-hydroxypropyl)palmitamide, (ii) a two step smooth transformation of the RC products into ACA and (iii) only one intermediate chromatographic purification step. The method offers a versatile approach to the preparation of ACA analogues, through the synthesis of an intermediate maleic anhydride with a vinylic group at the end of the aliphatic tail, a function that can be transformed through a thiol–ene coupling. Serendipitously, the disodium salt of 2-(9-(butylthio)nonyl)-3-methylmaleic acid, that we prepared as a representative sulfurated ACA analogue, was a more competent FTase inhibitor than ACA. This behaviour was analysed by a molecular docking study.

Novel Route to Chaetomellic Acid A and Analogues: Serendipitous Discovery of a more Competent FTase Inhibitor / Bellesia, Franco; Seoung ryoung, Choi; Fulvia, Felluga; Giuliano, Fiscaletti; Ghelfi, Franco; Menziani, Maria Cristina; Andrew F., Parsons; C., Dale Poulter; Roncaglia, Fabrizio; Massimo, Sabbatini; Domenico, Spinelli. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 1464-3391. - STAMPA. - 21:1(2013), pp. 348-358. [10.1016/j.bmc.2012.10.034]

Novel Route to Chaetomellic Acid A and Analogues: Serendipitous Discovery of a more Competent FTase Inhibitor

BELLESIA, Franco;GHELFI, Franco;MENZIANI, Maria Cristina;RONCAGLIA, Fabrizio;
2013

Abstract

A new practical route to chaetomellic acid A (ACA), based on the copper catalysed radical cyclization (RC) of (Z)-3-(2,2-dichloropropanoyl)-2-pentadecylidene-1,3-thiazinane, is described. Remarkably, the process entailed: (i) a one-pot preparation of the intermediate N-a-perchloroacyl-2-(Z)-alkyliden-1,3-thiazinanes starting from N-(3-hydroxypropyl)palmitamide, (ii) a two step smooth transformation of the RC products into ACA and (iii) only one intermediate chromatographic purification step. The method offers a versatile approach to the preparation of ACA analogues, through the synthesis of an intermediate maleic anhydride with a vinylic group at the end of the aliphatic tail, a function that can be transformed through a thiol–ene coupling. Serendipitously, the disodium salt of 2-(9-(butylthio)nonyl)-3-methylmaleic acid, that we prepared as a representative sulfurated ACA analogue, was a more competent FTase inhibitor than ACA. This behaviour was analysed by a molecular docking study.
2013
21
1
348
358
Novel Route to Chaetomellic Acid A and Analogues: Serendipitous Discovery of a more Competent FTase Inhibitor / Bellesia, Franco; Seoung ryoung, Choi; Fulvia, Felluga; Giuliano, Fiscaletti; Ghelfi, Franco; Menziani, Maria Cristina; Andrew F., Parsons; C., Dale Poulter; Roncaglia, Fabrizio; Massimo, Sabbatini; Domenico, Spinelli. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 1464-3391. - STAMPA. - 21:1(2013), pp. 348-358. [10.1016/j.bmc.2012.10.034]
Bellesia, Franco; Seoung ryoung, Choi; Fulvia, Felluga; Giuliano, Fiscaletti; Ghelfi, Franco; Menziani, Maria Cristina; Andrew F., Parsons; C., Dale P...espandi
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/917290
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 10
social impact