Rotational Energy Barrier around the C1–C11 Single Bond in Lamellarins: A Study by Variable-Temperature NMR

Abstract

In order to estimate the free energy barrier to rotation around the C1–C11 single bond in lamellarins, new lamellarin analogues (1a), (1b), (2a), and (2b) possessing diastereotopic protons or carbons at the C1 aryl moiety were synthesized. Variable-temperature H and C NMR measurements of these analogues revealed that the free energy barriers to rotation around the C1–C11 axis in 5,6-saturated and 5,6-unsaturated lamellarins were around 72–74 and 83–87 kJ/mol, respectively. INTRODUCTION The lamellarins constitute an important class of natural products of marine origin. Up to now, approximately fifty lamellarins have been characterized since the first isolation of lamellarins A–D from Lamellaria sp. in 1985. These lamellarins exhibit a number of interesting biological activities such as potent cytotoxicity against cancer cell lines, multi-drug resistance (MDR) reversal activity, anti-HIV activity, topoisomerase I inhibitory activity, inhibition of mitochondrial function, and protein kinases inhibitory activity. Lamellarins possess a unique 14-phenyl-6H-[1]benzopyrano[4’,3’:4,5]pyrrolo[2,1-a]isoquinolin-6-one ring system (Figure 1). They are divided into two structural types different in the degree of unsaturation at 5,6-bond. The naturally occurring lamellarins are highly substituted by oxygen functionalities (OH and OMe) on this scaffold. The biological activities are dependent on the position and the number of OH and OMe groups. According to X-ray crystallographic analyses of several lamellarins, the aryl group attached to C1 is This paper is dedicated to Professor Dr. Victor Snieckus on the occasion of his 77 birthday. HETEROCYCLES, Vol. 88, No. 2, 2014 1121