Emergence of diversity and stereochemical outcomes in the biosynthetic pathways of cyclobutane-centered marine alkaloid dimers

Abstract

Covering: up to 2016Dictazoles and sceptrins are singular metabolites of marine origin. The present dichotomic case study provides a comprehensive perspective on these cyclobutane-centered alkaloids and their respective families. Indeed, their upstream and downstream chemistry are both treated herein. Relevant isolation reports and bio-inspired total syntheses are used to decipher the currently admitted biosynthetic hypotheses as well as the emergence of diversity in the two series. This review proposes a transversal vision of the topic, where most aspects of natural product chemistry have a critical importance.

[2+2] Photodimerization of Stilbazoles Promoted by Oxalic Acid in Suspension

“…In this context,aversatile and flexibles creening strategy to determine rapidlyt he right additives and to efficiently perform the photocycloaddition in av ery simple manner would be highly desirable, especially for cost-effective and large-scale production of structurally and biologically relevant cycloadducts [11] with well-defined regio-and stereochemistry.…”

“…Other carboxylic acids, such as higher analogues (malonic and succinic acids b-c,e ntries 3, 4, Ta ble 1), unsaturated acids (maleicand fumaricacids d-e,entries 5, 6, Table 1), benzeneoligocarboxylic acids f-k (entries 7-12, Ta ble 1) as well as simple monocarboxylic acid,such as phenylacetic acid l (entry 13), displayede ither lower efficiency( leadingt ol ower yields but the reaction mixtures remained rather clean, entries 3, 6, 7, 9, 10, Ta ble 1) or unsuitability as additive due to the formationo f complex mixtures of other isomeric adducts and unidentified side products (entries 4,5,8,(11)(12)(13)Ta ble 1).…”

DNA‐Templated [2+2] Photocycloaddition: A Straightforward Entry into the Aplysinopsin Family of Natural Products

“…Hence,starting from three different natural aplysinopsinderived monomers,wewere able to access four cyclobutanecentered skeletons,i ncluding natural dictazole B. Interestingly,t he homodimer 2a could also be further converted to yet another natural product, tubastrindole B, through ar ingexpansion cascade involving the formation of Mancinis intermediate (Scheme 1), thus showcasing the possible generalization of this approach to the entire aplysinopsin family of natural products. [34] In summary,w ed eveloped an unprecedented DNAtemplated [2+ +2] photodimerization process and demonstrated its synthetic utility by applying it to the synthesis of spiro-fused cyclobutane-containing compounds including the natural heterodimer dictazole B. Thel atter was obtained in 16 %i solated yield, which significantly improved the results obtained under the standard solvent-free conditions.M oreover, by applying solid-state supramolecular principles ascertained by CD spectroscopy,w eh ave shown that DNAc ould be au seful template to build aggregates with photoreactive units.M ost importantly,w eb elieve that this method is not limited to the aplysinopsins.I ndeed, by fine-tuning the specific interaction between DNAa nd any given monomer, we should be able to extend the scope of the method and thus pave the way to new target-oriented syntheses.…”

DNA‐Templated [2+2] Photocycloaddition: A Straightforward Entry into the Aplysinopsin Family of Natural Products

“…Hence, starting from three different natural aplysinopsin-derived monomers, we were able to access four cyclobutane-centered skeletons, including natural dictazole B. Interestingly, the homodimer 2a could also be further converted to yet another natural product, tubastrindole B, through a ring-expansion cascade involving the formation of Mancini's intermediate (Scheme 1), thus showcasing the possible generalization of this approach to the entire aplysinopsin family of natural products. [34] In summary, we've developed an unprecedented DNA-templated [2+2] photodimerization process and demonstrated its synthetic utility by applying it to the synthesis of spiro-fused cyclobutane-containing compounds including the natural heterodimer dictazole B. The latter was obtained in 16% isolated yield, which significantly improved the results obtained under the standard solvent-free conditions.…”