15778-62-8Relevant academic research and scientific papers
Designing new analogs for streamlining the structure of cytotoxic lamellarin natural products
Tangdenpaisal, Kassrin,Worayuthakarn, Rattana,Karnkla, Supatra,Ploypradith, Poonsakdi,Intachote, Pakamas,Sengsai, Suchada,Saimanee, Busakorn,Ruchirawat, Somsak,Chittchang, Montakarn
, p. 925 - 937 (2015/03/31)
Despite the therapeutic potential of marine-derived lamellarin natural products, their preclinical development has been hampered by their lipophilic nature, causing very poor aqueous solubility. In order to develop more drug-like analogs, their structure was streamlined in this study from both the cytotoxic activity and lipophilicity standpoints. First, a modified total synthetic route was successfully devised to construct a library of 59 systematically designed lamellarin analogs, which were then subjected to cytotoxicity and log P determinations. Along with the 25 first-generation lamellarins previously synthesized in our laboratory, the structure-activity and structure-lipophilicity relationships were extensively evaluated. Our results clearly indicated the additional structural requirements around the lamellarin skeleton which, when combined with those reported previously, can provide invaluable guidance for further modifications to increase the aqueous solubility of these compounds.
Total synthesis of natural and unnatural lamellarins with saturated and unsaturated D-rings
Ploypradith, Poonsakdi,Petchmanee, Thaninee,Sahakitpichan, Poolsak,Litvinas, Nichole D.,Ruchirawat, Somsak
, p. 9440 - 9448 (2007/10/03)
(Chemical Equation Presented) Twenty-eight natural and unnatural lamellarins with either a saturated or an unsaturated D-ring were synthesized according to our developed synthetic route. The key step involved the Michael addition/ring closure (Mi-RC) of the benzyldihydroisoquinoline and α-nitrocinnamate derivatives, which provided the 2-carboethoxypyrrole intermediates in moderate to good yields (up to 78% yield). Subsequent hydrogenolysis/lactonization furnished lamellarins with a saturated D-ring in excellent yields (up to 93% yield). DDQ oxidation of the saturated lamellarin acetates led directly to the corresponding unsaturated analogues in 54-95% yield. In addition, only two steps in our developed strategy require column chromatography.
Structure and synthesis of goudotianine, a new 7-methyldehydroaporphine from Guatteria goudotiana
Castedo,Granja,Rodriguez de Lera,Villaverde
, p. 1561 - 1566 (2007/10/02)
Total synthesis of 2,9-dihydroxy-1,3-dimethoxy-7-methyl-6a,7-dehydroaporphine 1a and 3,9-dihydroxy-1,2-dimethoxy-7-methyl-6a,7-dehydroaporphine 1b are described. Direct comparison of both with natural goudotianine isolated from Guatteria goudotiana R.E. Fries showed the latter to be identical with 1b.
