Total synthesis of cruentaren B.
A convergent total synthesis of the cytotoxic natural product cruentaren B is completed in 26 steps (longest linear sequence) with an overall yield of 7.1%. For the construction of the C1-C11 benzolactone fragment of the molecule, the key steps used were O-methylation, using a Mitsunobu reaction, a Stille coupling method to construct the C7-C8 bond, and a Brown's asymmetric crotylboration reaction for the direct enantioselective installation of the two chiral centers present in this fragment. For diastereoselective installation of the chiral centers in the C12-C20 polyketide fragment, an Evans syn aldol reaction on a chiral aldehyde, derived from methyl (R)-3-hydroxyl-2-methylpropionate, and subsequently a Mukaiyama aldol reaction were employed. For the construction of the C21-C28 tail, a "non-Evans" syn aldol reaction was used. The three fragments were coupled by an SN2 reaction and a Wittig olefination reaction followed by standard functional group manipulations to furnish the target molecule.
Chakraborty
Tushar Kanti
TK
Indian Institute of Chemical Technology,Hyderabad 500007, India. chakraborty@iict.res.in
Chattopadhyay
Amit Kumar
AK
D049934:Isocoumarins / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure
D049934:Isocoumarins; C516695:cruentaren B