Convergent Total Synthesis of Lamellarins and Their Congeners

Abstract

A convergent total synthesis of lamellarins S and Z is described. The synthesis features a halogen dance of an easily accessible α,β-dibromopyrrole promoted by an ester moiety. The resultant β,β'-dibromopyrrole undergoes a ligandcontrolled Suzuki-Miyaura coupling to provide a range of diarylated pyrrole derivatives. The established synthetic method was also applicable to the synthesis of ningalin B, and lukianols A and B.

Concise and Scalable Total Syntheses of Lamellarin Z and other Natural Lamellarins

“…Also, a further extension to the pentacyclic lamellarin scaffolds has been demonstrated through a one-pot CDC reaction, thereby enabling a 5-step total synthesis of lamellarins Z and S with the highest overall yields of 27 % and 26 % respectively, reported till date in the literature. [12,23] Further, the 5-step synthesis of lamellarins G and L accomplished with an overall yield of 26 % each, compares reasonably well, either in terms of step economy or overall yield with many of the earlier reported synthesis. Even the 6-step synthesis of lamellarins N and D accomplished with overall yields of 24 % and 20 % respectively compares satisfactorily with the previous synthetic reports.…”

“…[18,19] Next, our attention turned towards the synthesis of lamellarins G, L, and N. As highlighted in Scheme 4, a similar reaction sequence as described above was adopted for the other lamellarins. The pyrrole ester (12) accessed from the annulation of the aziridine-2-carboxylate 5 with β-bromo-βnitrostyrene (6 b), was subjected to saponification and subsequently, a coupling of the resultant acid (13) with 9 b,c [17,20] to arrive at the phenyl tethered esters (14 a,b) in excellent yields. Next, the crucial Pd-mediated CDC reaction in presence of Cu (OAc) 2 as cooxidant was executed on 14 a,b, to arrive at the pentacyclic lactones (15 a,b) in moderate yields.…”

Synthesis of lamellarin R, lukianol A, lamellarin O and their analogues

“…A key feature in the synthesis of lamellarin alkaloids type III is the construction of the aryl-substituted pyrrole ring, which can be categorized into two different synthetic approaches, that is, functionalization of a simple pyrrole core and synthesis of the functionalized pyrrole moiety from the appropriate precursors. The former is represented by the works of Banwell, 6 Iwao, 7 Wong 8 and Okano's groups, 9 whereas the latter is exemplied by Boger,10 Vazquez, 11 F} urstner, 12 Jia, 13 Hwu, 14 Iwao, 15 and Yang's groups. 16 While the total synthesis of lamellarin alkaloids type III has been documented by the aforementioned researchers, the development of more efficient and greener synthesis of these natural products along with their analogues leaves more room for improvement.…”

Concise and Scalable Total Syntheses of Lamellarin Z and other Natural Lamellarins: Regiocontrolled Assembly of the Central Pyrrole Core and Cross Dehydrogenative Coupling Enroute to the Pentacyclic Coumarin-Pyrrole-Isoquinoline Scaffold

“…Our continuing interest in marine pyrrole alkaloids (MPAs) [8,10] gave us the realization that despite numerous synthetic efforts towards various members of the lamellarin family, there still exist some members for which either no chemical synthesis subsists or there are very few reports. This prompted us to further validate the generality and flexibility of our already reported synthetic strategy towards lamellarins by demonstrating its applicability for the total synthesis of lamellarins Z [11,12], G, and S besides other frequently targeted biologically significant lamellarins L, N and D. In this article, we present the details of our synthetic investigation in the context of these natural marine pyrrole alkaloids (MPAs).…”