Complex Polypropionates from a South China Sea Photosynthetic Mollusk: Isolation and Biomimetic Synthesis Highlighting Novel Rearrangements

Abstract

Placobranchus ocellatus, regarded as a "solar-powered" sacoglossan mollusk, is well known to produce diverse and complex γ-pyrone polypropionates. Unexpectedly, in this study, the chemical investigation of P. ocellatus from the South China Sea led to the discovery of ocellatusones A−D, a series of racemic non-γpyrone polyketides with novel skeletons, characterized by a bicyclo[3.2.1]octane (1, 2), a bicyclo[3.3.1]nonane (3) or a mesitylene-substituted dimethylfuran-3(2H)-one core (4). Extensive spectroscopic analysis, quantum chemical computation, chemical synthesis, and/or X-ray diffraction analysis were used to determine the structure and absolute configuration of the new compounds, including each enantiomer of racemic compounds 1−4 after chiral HPLC resolution. An important array of new and diversitygenerating rearrangements is proposed to explain the biosynthesis of these unusual compounds based on careful structural analysis and comparison with six known co-occurring γ-pyrones (5−10). Furthermore, the successful biomimetic synthesis of ocellatusone A (1) from its γ-pyrone precursor (5) confirmed the biosynthetic relationship of these two compounds and the proposed rearrangement through an unprecedented acid promoted cascade reaction. Besides, an initially untargeted semisynthetic product, polycyclic lactone 11 with another novel carbocyclic skeleton was proved to be naturally occurring in the mollusk by comparative LC-MS/MS analysis, which provides a strategy to fish a vast number of novel trace components in Nature.

Xishaeleganins A–D, Sesquiterpenoid Hydroquinones from Xisha Marine Sponge Dactylospongia elegans

“…Among them, the known compounds were readily identified as dactyloquinone C (12) [25], polyfibrospongol A (14) [26], dictyoceratin A (15) [27], dictyoceratin B (16) [27], dictyoceratin C (17) [28], dactyloquinone A (18) [29], dactyloquinone B (19) [29], ilimaquinone (20) [30], epi-ilimaquinone (21) [31], dactyloquinone D (22) [25], and dactyloquinone As part of our ongoing project towards the isolation of biologically active compounds from Chinese marine benthic invertebrates [18][19][20], a batch of Dactylospongia elegans sponges was collected off the coast of Xisha Island, Hainan Province, China, and chemically investigated. Dactylospongia elegans sponges belonging to the family Thorectida (order Dictyoceratida, class Demospongiae, and phylum Porifera) are prolific sources of biologically active compounds spanning a wide range of structural classes, from meroterpenoids [21,22], steroids [23], to diterpenoids [24], etc.…”

“…Among them, the known compounds were readily identified as dactyloquinone C (12) [25], polyfibrospongol A (14) [26], dictyoceratin A (15) [27], dictyoceratin B (16) [27], dic-tyoceratin C (17) [28], dactyloquinone A (18) [29], dactyloquinone B (19) [29], ilimaquinone (20) [30], epi-ilimaquinone (21) [31], dactyloquinone D (22) [25], and dactyloquinone E (23) [25], by comparing their NMR data and optical rotation values with those reported in the literature.…”

Structural and Biological Insights into the Hot‐Spot Marine Natural Products Reported from 2012 to 2021

“…The biosynthetic pathway has been confirmed by its biomimetic semi‐ synthesis. [ 212 ] 9‐Isocyanoneoallopupukeanane ( 235 ), obtained from an Indo‐Pacific nudibranch Phyllidiella pustulosa , is a sesquiterpene isonitrile exhibiting micromolar antimalarial activities. [ 213 ] Cistobislactones A ( 236 ) and B ( 237 ), from a marine octopus Cistopus indicus , are two unprecedented sixteen‐membered spiro‐linked macrocylic bislactones showing anti‐inflammatory activities against arachidonate 5‐lipoxygenas.…”

Natural Polypropionates in 1999–2020: An Overview of Chemical and Biological Diversity

“…Except for the three pairs of carbon homocyclic PPs (±)- 15 –(±)- 17 , the mollusk P. ocellatus also produced a pair of furanone-containing analogues (±)- 106 [ 16 ], which represents a unique dimethylfuran-3( 2H )-one nucleus connected with a mesitylene moiety ( Figure 15 ). An X-ray diffraction was carried out to confirm its racemic nature by a P-1 space group.…”

“…Three pairs of enantiomers (±)-ocellatusones A-C (15)(16)(17), constructing a bicyclo[3.2.1]octane or bicyclo [3.3.1]nonane, were discovered from a South-China-Sea-derived photosynthetic mollusk Placobranchus ocellatus [16]. These represent the most complex carbon homocycle containing PPs to date (Figure 4).…”