Total synthesis of natural and unnatural lamellarins with saturated and unsaturated D-rings.
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 alpha-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.
Ploypradith
Poonsakdi
P
Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, Vipavadee-Rangsit Highway, Bangkok, Thailand 10210. poonsakdi@cri.or.th
Petchmanee
Thaninee
T
Sahakitpichan
Poolsak
P
Litvinas
Nichole D
ND
Ruchirawat
Somsak
S
D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry
D003374:Coumarins; D006576:Heterocyclic Compounds, 4 or More Rings; D007546:Isoquinolines; C455554:lamellarin D