A Chemoenzymatic Total Synthesis of (+)-Amabiline

Abstract

The readily available and enzymatically derived cis-1,2-dihydrocatechol 3 has been converted, over 15 steps, into (+)-amabiline, the non-natural enantiomeric form of a crinine-type alkaloid.

The Exploitation of Enzymatically‐Derived cis‐1,2‐Dihydrocatechols and Related Compounds in the Synthesis of Biologically Active Natural Products

“…Given the capacity it provides to construct quaternary carbon centers in a predictable manner, the Eschenmoser‐Claisen rearrangement reaction has also played a pivotal role in our development of total syntheses of the clinically‐deployed anti‐Alzheimer's drug galanthamine ( 187 ) and various analogues from starting materials such as 1 (X=Br) . When used in conjunction with the Suzuki‐Miyaura cross‐coupling, intramolecular S N ′ and Pictet‐Spengler reactions, the Eschenmoser‐Claisen rearrangement has also allowed us to establish a total synthesis of (+)‐amabiline ( 188 ), the enantiomer of a crinine alkaloid …”

Efficient syntheses of (−)-crinine and (−)-aspidospermidine, and the formal synthesis of (−)-minfiensine by enantioselective intramolecular dearomative cyclization

“…Methanolysis of 15 led to the formation of two natural products, buphanisine ( 16 ) 8h , 9b and epibuphanisine ( 17 ). 16 Alternatively, the reduction of 15 with LiEt 3 BH followed by dihydroxylation led to the formation of amabiline ( 18 ) 8c , 17 in 50% overall yield. Thus, a series of crinine-type alkaloids were conveniently synthesized using this synthetic route.…”

The Application of Dioxygenase‐Based Chemoenzymatic Processes to the Total Synthesis of Natural Products

“…compound 33,h as also been prepared from compound 2 (X = Br) by employing as equence involving cis-dihydroxylation, Suzuki-Miyaura cross-coupling, Eschenmoser-Claisenr earrangement, intramolecular S N ' and Pictet-Spengler reactions. [34] Our work in such areas has revealed that certain stereochemical arrays are not readily accessible through manipulationo f metabolites of the general form 2 and so we have developed complementary building blocks such as the polyoxygenated cyclohexenone 34 from (+ +)-tartaric acid [35] and elaborated this to the antifungal deoxyaminocyclitol nabscessin B ( 35). [36] Given the equally ready availability of (À)-tartarica cid, these sorts of "chirons" represent very useful new ones for our work in this area.…”