Natural products derived from marine microorganisms have received great attention as a potential resource of new compound entities for drug discovery. The unique marine environment brings us a large group of sulfur-containing natural products with abundant biological functionality including antitumor, antibiotic, anti-inflammatory and antiviral activities. We reviewed all the 484 sulfur-containing natural products (non-sulfated) isolated from marine microorganisms, of which 59.9% are thioethers, 29.8% are thiazole/thiazoline-containing compounds and 10.3% are sulfoxides, sulfones, thioesters and many others. A selection of 133 compounds was further discussed on their structure–activity relationships, mechanisms of action, biosynthesis, and druggability. This is the first systematic review on sulfur-containing natural products from marine microorganisms conducted from January 1987, when the first one was reported, to December 2020.

Four new bisabolane-type sesquiterpenoids, aspergiterpenoid A (1), (−)-sydonol (2), (−)-sydonic acid (3), and (−)-5-(hydroxymethyl)-2-(2′,6′,6′-trimethyltetrahydro-2H- pyran-2-yl)phenol (4) together with one known fungal metabolite (5) were isolated from the fermentation broth of a marine-derived fungus Aspergillus sp., which was isolated from the sponge Xestospongia testudinaria collected from the South China Sea. Four of them (1–4) are optically active compounds. Their structures and absolute configurations were elucidated by using NMR spectroscopic techniques and mass spectrometric analysis, and by comparing their optical rotations with those related known analogues. Compounds 1–5 showed selective antibacterial activity against eight bacterial strains with the MIC (minimum inhibiting concentrations) values between 1.25 and 20.0 µM. The cytotoxic, antifouling, and acetylcholinesterase inhibitory activities of these compounds were also examined.

An efficient dehydrative S _N 1-type reaction of indolyl alcohols with diverse nucleophiles was developed using water as the solvent, affording versatile 3-indolyl derivatives in high yields. The advantages of being catalyst-free, environmentally benign, and wide substrate scope make it a promising method for preparation of indolyl compounds.

Metabolites from marine organisms have proven to be a rich source for the discovery of multiple potent bioactive molecules with diverse structures. In recent years, we initiated a program to investigate the diversity of the secondary metabolites from marine invertebrates and their symbiotic microorganisms collected from the South China Sea. In this review, representative cases are summarized focusing on molecular diversity, mining, and application of natural products from these marine organisms. To provide a comprehensive introduction to the field of marine natural products, we highlight typical molecules including their structures, chemical synthesis, bioactivities and mechanisms, structure–activity relationships as well as biogenesis. The mining of marine-derived microorganisms to produce novel secondary metabolites is also discussed through the OSMAC strategy and via partial chemical epigenetic modification. A broad prospectus has revealed a plethora of bioactive natural products with novel structures from marine organisms, especially from soft corals, gorgonians, sponges, and their symbiotic fungi and bacteria.

One new phenylalanine derivative 4′-OMe-asperphenamate (1), along with one known phenylalanine derivative (2) and two new cytochalasins, aspochalasin A1 (3) and cytochalasin Z24 (4), as well as eight known cytochalasin analogues (5–12) were isolated from the fermentation broth of Aspergillus elegans ZJ-2008010, a fungus obtained from a soft coral Sarcophyton sp. collected from the South China Sea. Their structures and the relative configurations were elucidated using comprehensive spectroscopic methods. The absolute configuration of 1 was determined by chemical synthesis and Marfey’s method. All isolated metabolites (1–12) were evaluated for their antifouling and antibacterial activities. Cytochalasins 5, 6, 8 and 9 showed strong antifouling activity against the larval settlement of the barnacle Balanus amphitrite, with the EC₅₀ values ranging from 6.2 to 37 μM. This is the first report of antifouling activity for this class of metabolites. Additionally, 8 exhibited a broad spectrum of antibacterial activity, especially against four pathogenic bacteria Staphylococcus albus, S. aureus, Escherichia coli and Bacillus cereus.

Three new phenolic bisabolane-type sesquiterpenoids: (+)-methyl sydowate (1), 7-deoxy-7,14-didehydrosydonic acid (2), and 7-deoxy-7,8-didehydrosydonic acid (3), together with two known fungal metabolites were isolated from the fermentation broth of a marine-derived fungus Aspergillus sp., which was isolated in turn from a gorgonian Dichotella gemmacea collected from the South China Sea. Their structures were elucidated by combined spectroscopic methods, and the structure of 1 was further confirmed by single-crystal X-ray data.