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Reported biological activities of Stemona natural products, such as antitussive activity, inspired the development of synthetic methods to access several alkaloids within this family and in so doing develop a general route to the core skeleta shared by the class of natural products. The chemistry was subsequently adapted to afford a series of analogue sets bearing simplified, diverse Stemona-inspired skeleta. Over 100 of these analogues were subjected to general G protein-coupled receptor profiling along with the known antitussive compound, neostenine; this led to the identification of hit compounds targeting several receptor types. The particularly rich hit subset for sigma receptors was expanded with two focused library sets, which resulted in the discovery of a fully synthetic, potent chemotype of sigma ligands. This collaborative effort combined the development of synthetic methods with extensive, flexible screening resources and exemplifies the role of natural products in bioactivity mining. |
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sltmac(½ð±Ò+1): лл½»Á÷~~ 2011-06-03 20:36:58
Mally89(½ð±Ò+1): Âù³¤µÄ£¬ÔÙÌíÒ»¸ö£¡~ 2011-06-03 21:22:18
ÑÌÔÆÌýÓê(½ð±Ò+10, ·ÒëEPI+1): лл 2011-06-04 11:11:37
sltmac(½ð±Ò+1): лл½»Á÷~~ 2011-06-03 20:36:58
Mally89(½ð±Ò+1): Âù³¤µÄ£¬ÔÙÌíÒ»¸ö£¡~ 2011-06-03 21:22:18
ÑÌÔÆÌýÓê(½ð±Ò+10, ·ÒëEPI+1): лл 2011-06-04 11:11:37
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Reported biological activities of Stemona natural products, such asantitussive activity, inspired the development of synthetic methodsto access several alkaloids within this family and in so doing developa general route to the core skeleta shared by the class of naturalproducts. ±¨µÀµÄ°Ù²¿ÊôÖÐÓÐÉúÎï»îÐÔµÄÌìÈ»²úÎÀýÈ磬ÓÐÕò¿È»îÐԵϝºÏÎÆô·¢Á˱¾ÊôÖм¸¸öÉúÎï¼îµÄºÏ³É·½·¨£¬²¢·¢Õ¹ÁËÒ»Ìõ³£¹æºÏ³ÉÕâЩÌìÈ»²úÎïºËÐĽṹµÄ·½·¨¡£ The chemistry was subsequently adapted to afford a seriesof analogue sets bearing simplified, diverse Stemona-inspiredskeleta. Ëæºó»¯Ñ§·¢Õ¹ÁËһϵÁеÄÀàËÆµÄ¼ò»¯ÁËÀàËÆµÄ¹ØÏµ¼¯ºÏ¡£ Over 100 of these analogues were subjected to generalG protein-coupled receptor profiling along with the known antitussivecompound, neostenine; this led to the identification ofhit compounds targeting several receptor types. ³¬¹ý100ÖÖÀàËÆÎïÎ§ÈÆÒÑÖªµÄÕò¿È»îÐÔ»¯ºÏÎïneostenineµÄ½á¹¹ÔÚÒ»Æð×é³ÉÁËGµ°°×żÁªÊÜÌ壬´Ó¶ø¼ø¶¨³öÒ©ÎïÊǽø¹¥ÄÇÖÖÊÜÌå¡£ The particularlyrich hit subset for sigma receptors was expanded with two focusedlibrary sets, which resulted in the discovery of a fully synthetic,potent chemotype of sigma ligands. Ã÷È·µØ£¬±¥ºÍ¶Ô ¦Ò-ÊÜÌåµÄ½ø¹¥ÑÓÉìµ½Á½¸öרעµÄ¼¯ºÏ¿â£¬´Ó¶ø·¢ÏÖÁËÒ»¸öÍêÕûµÄºÏ³ÉÎǿЧµÄ¦Ò-ÅäÌå¡£ This collaborative effortcombined the development of synthetic methods with extensive,flexible screening resources and exemplifies the role of natural productsin bioactivity mining. ÕâÖÖÐ×÷µÄ£¬»ìºÏµÄºÏ³É·¨µÄ·¢ÏÖ¿ÉÒԹ㷺µÄ£¬Áé»îµÄɸѡ×ÊÔ´£¬²¢ÇÒÀýÖ¤ÌìÈ»²úÎïµÄÉúÎï»îÐÔ¡£ |
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