Saturated heterocycles are found in numerous therapeutics as well as bioactive natural products and are abundant in many medicinal and agrochemical compound libraries. To access new chemical space and function, many methods for functionalization on the periphery of these structures have been developed. Comparatively fewer methods are known for restructuring their core framework. Herein, we describe a visible light-mediated ring contraction of α-acylated saturated heterocycles. This unconventional transformation is orthogonal to traditional ring contractions, challenging the paradigm for diversification of heterocycles including piperidine, morpholine, thiane, tetrahydropyran, and tetrahydroisoquinoline derivatives. The success of this Norrish Type II variant rests on reactivity differences between photoreactive ketone groups in specific chemical environments. This strategy was applied to late-stage remodeling of pharmaceutical derivatives, peptides, and sugars.

Anew bicyclic diterpenoid, benditerpenoic acid, was isolated from soil-dwelling Streptomyces sp.( CL12-4). We sequenced the bacterial genome,i dentified the responsible biosynthetic gene cluster,v erified the function of the terpene synthase,a nd heterologously produced the core diterpene. Comparative bioinformatics indicated this Streptomyces strain is phylogenetically unique and possesses nine terpene synthases.The absolute configurations of the new trans-fused bicyclo-[8.4.0]tetradecanes were achieved by extensive spectroscopic analyses,i ncluding Moshersa nalysis,J -based coupling analysis,a nd computations based on sparse NMR-derived experimental restraints.I nterestingly,b enditerpenoic acid exists in two distinct ring-flipped bicyclic conformations with ar otational barrier of % 16 kcal mol À1 in solution. The diterpenes exhibit moderate antibacterial activity against Gram-positive bacteria including methicillin and multi-drug resistant Staphylococcus aureus.This is arare example of an eunicellane-type diterpenoid from bacteria and the first identification of ad iterpene synthase and biosynthetic gene cluster responsible for the construction of the eunicellane scaffold.

Saturated cyclic amines (aza-cycles) are ubiquitous structural motifs found in pharmaceuticals, agrochemicals, and bioactive natural products. Given their importance, methods that directly functionalize aza-cycles are in high demand. Herein, we disclose a fundamentally different approach to functionalizing cyclic amines which relies on C−C cleavage and attendant cross-coupling. The initial functionalization step is the generation of underexplored N-fused bicyclo α-hydroxy-β-lactams under mild, visible light conditions using a Norrish−Yang process to affect α-functionalization of saturated cyclic amines. This approach is complementary to previous methods for the C−H functionalization of aza-cycles and provides unique access to various cross-coupling adducts. In the course of these studies, we have also uncovered an orthogonal, base-promoted opening of the N-fused bicyclo α-hydroxy-β-lactams. Computational studies have provided insight into the origin of the complementary C−C cleavage processes.

Mutualisms between cnidarian hosts and dinoflagellate endosymbionts are foundational to coral reef ecosystems. These symbioses are often re-established every generation with high specificity, but gaps remain in our understanding of the cellular mechanisms that control symbiont recognition and uptake dynamics. Here, we tested whether differences in glycan profiles among different symbiont species account for the different rates at which they initially colonize aposymbiotic polyps of the model sea anemone Aiptasia (Exaiptasia pallida). First, we used a lectin array to characterize the glycan profiles of colonizing Symbiodinium minutum (ITS2 type B1) and noncolonizing Symbiodinium pilosum (ITS2 type A2), finding subtle differences in the binding of lectins Euonymus europaeus lectin (EEL) and Urtica dioica agglutinin lectin (UDA) that distinguish between high-mannoside and hybrid-type protein linked glycans. Next, we enzymatically cleaved glycans from the surfaces of S. minutum cultures and followed their recovery using flow cytometry, establishing a 48–72 h glycan turnover rate for this species. Finally, we exposed aposymbiotic host polyps to cultured S. minutum cells masked by EEL or UDA lectins for 48 h, then measured cell densities the following day. We found no effect of glycan masking on symbiont density, providing further support to the hypothesis that glycan-lectin interactions are more important for post-phagocytic persistence of specific symbionts than they are for initial uptake. We also identified several methodological and biological factors that may limit the utility of studying glycan masking in the Aiptasia system.

The genetically encoded, small-molecule chemical diversity of filamentous fungi is still largely unexplored and represents an attractive source for the discovery of new compounds. Here we report the production of new chlorinated bianthrones from coculture of two different developmental stages, or morphs, of a marine alga-derived Aspergillus alliaceus (teleomorph: Petromyces alliaceus) strain. The vegetative stage (asexual morph) can be separated from the morph that switched to sexual development (sclerotial morph); both produce distinct secondary metabolite patterns. Ochratoxin (1) was mainly found in the monoculture of the sclerotial morph, while the anthraquinone pigment nalgiovensin (2) was produced by the asexual morph. Surprisingly, combining cultures from both developmental stages in a coculture experiment changed the metabolite profile drastically. The chlorinated congener nalgiolaxin (3) was abundant, and newly produced bianthrones were found. Allianthrone A (4) and its two diastereomers [allianthrones B (5) and C (6)] were isolated, and the new structures were determined by extensive NMR spectroscopic analysis, supported by optical properties and X-ray crystallography. All metabolites were tested in antibiotic and cytotoxicity assays, and allianthrone A (4) showed weak cytotoxic activity against the HCT-116 colon cancer and SK-Mel-5 melanoma cell lines.