Synthesis of lamellarin alkaloids using orthoester-masked α-keto acids

Abstract

Enolate arylation of a protected pyruvate is used as a key step in the short and efficient syntheses of the lamellarins.

Marine Pyrrole Alkaloids

“…In 2012, a new bromopyrrole, 4-bromo-N-(butoxymethyl)-1H-pyrrole-2-carboxamide (192), featuring an unusual ether group in its side chain, could be isolated from the marine sponge Agelas mauritiana (Figure 24) [233]. (196)(197)(198)(199).…”

“…A new class of bromopyrrole pigments derived from bromotyrosine were isolated from the marine ciliate Pseudokeronopsis riccii in 2010 and were named keronopsamides A-C (201-203) (Figure 25) [236]. (196)(197)(198)(199).…”

“…Further structurally similar halopyrroles 193-199 possessing different substituents at their amide side chains were isolated from the Indonesian marine sponges Agelas linnaei (Figure 24) [234]. While mauritamide D (193), 4-(4,5-dibromo-1-methylpyrrole-2carboxamido)-butanoic acid (194), and agelanin B (195) were inactive against L1578Y mouse lymphoma cell lines, the tyramine-unit bearing agelanesins A-D (196)(197)(198)(199) showed prominent to good activity with IC 50 values between 9.25 µM and 16.76 µM in this assay. The authors mentioned that the cytotoxicity of the agelanesins 196-199 is interconnected with the degree of bromination of the pyrrole ring, resulting in an increased reactivity for the monobrominated agelanesins A (196) and B (197) compared to 198 and 199 [234].…”

“…Figure 24. Simple bromopyrrole alkaloids 192-195 and structural similar agelanesins A-D(196)(197)(198)(199).…”

Diethyl Azodicarboxylate-Promoted Oxidative [3 + 2] Cycloaddition for the Synthesis of Pyrrolo[2,1-a]isoquinolines

“…These marine natural alkaloids, bearing a pyrrolo­[2,1- a ]­isoquinoline core, were proven to have a wide spectrum of pharmacological activities. , Some lamellarins exhibited potent antitumor activity including multidrug resistant cell lines by inhibition, , for example, human topoisomerase I . Also, sulfated lamellarins such as lamellarin α-20-sulfate were expected to be selective human immunodeficiency virus integrase inhibitors at noncytotoxic concentrations. , To better understand these attractive compounds and their biological activities, as early as 1997, a number of laboratories realized the total synthesis. , Furthermore, the construction of the pyrrolo­[2,1- a ]­isoquinoline core has become a crucial issue, for which a variety of synthetic methods have been developed, including 1,3-dipolar cycloaddition, ,, oxidative dimerization, and double-barreled Heck cyclization, providing a wealth of ideas for the synthesis of natural and non-natural lamellarins.…”