Asymmetric Synthesis of Four Stereoisomers of 2,2-Dimethyl-3-hydroxy-4-(1′-angeloyloxy)-6-acetylchromane from Ageratina grandifolia and Plausible Absolute Stereochemistry of the Natural Product

2,2-Dimethyl-3-hydroxy-4-(1′-angeloyloxy)-6-acetylchromane is a natural product isolated from Ageratina grandifolia that exhibits inhibitory activity against yeast α-glucosidase. Initially, its structure was proposed to be 4-hydroxy-3-((S)-1′-angeloyloxy-(R)-2′,3′-epoxy-3′-methyl)butylacetophenone with an epoxide, but the structure was later revised to 2,2-dimethyl-3R-hydroxy-4S-(1-angeloyloxy)-6-acetylchromane. In this study, we present a total synthesis of 2,2-dimethyl-3-hydroxy-4-(1′-angeloyloxy)-6-acetylchromane from A. gradifolia and its stereoisomers. The key features of their synthesis include Sharpless asymmetric dihydroxylation of a readily available benzopyran substrate and subsequent Mitsunobu or Steglich reaction to provide both cis- and trans-isomers with chiral control. The absolute stereochemistry of the natural product was determined to be 2,2-dimethyl-3S-hydroxy-4R-(1′-angeloyloxy)-6-acetylchromane based on optical rotations of the synthesized compounds. The absolute configuration of the synthesized stereoisomers was confirmed by Mosher ester analysis. In addition, we provided ECD spectra for the four stereoisomers, which will allow verification of the absolute configuration of the natural product. Synthesis of all four stereoisomers of 2,2-dimethyl-3-hydroxy-4-(1′-angeloyloxy)-6-acetylchromane would facilitate the exploration of their potential biomedical applications

Mohangamides A and B, New Dilactone-Tethered Pseudo-Dimeric Peptides Inhibiting <i>Candida albicans</i> Isocitrate Lyase

Mohangamides A and B (<b>1</b>–<b>2</b>) were discovered from a marine <i>Streptomyces</i> sp. collected in an intertidal mud flat. The structures of the compounds were elucidated as novel dilactone-tethered pseudodimeric peptides bearing two unusual acyl chains and 14 amino acid residues based on comprehensive spectroscopic analysis. The absolute configurations of the mohangamides were determined by chemical derivatizations, followed by chromatographic and spectroscopic analyses. Mohangamide A displayed strong inhibitory activity against <i>Candida albicans</i> isocitrate lyase

Mohangic Acids A–E, <i>p</i>‑Aminoacetophenonic Acids from a Marine-Mudflat-Derived <i>Streptomyces</i> sp.

Mohangic acids A–E (<b>1</b>–<b>5</b>) were isolated from a marine <i>Streptomyces</i> sp. collected from a mudflat in Buan, Republic of Korea. Comprehensive spectroscopic analysis revealed that the mohangic acids are new members of the <i>p</i>-aminoacetophenonic acid class. The relative and absolute configurations of the mohangic acids were determined by <i>J</i>-based configuration analysis and by the application of bidentate chiral NMR solvents followed by ¹³C NMR analysis, chemical derivatization, and circular dichroism spectroscopy. Mohangic acid E (<b>5</b>), which is the first glycosylated compound in the <i>p</i>-aminoacetophenonic acid family, displayed significant quinone reductase induction activity

WS9326H, an Antiangiogenic Pyrazolone-Bearing Peptide from an Intertidal Mudflat Actinomycete

WS9326H (<b>1</b>), a new cyclic peptide, was isolated from a mudflat-derived <i>Streptomyces</i> strain. Based on analysis by 1D/2D NMR, UV spectroscopy, and mass spectrometry, compound <b>1</b> was determined to have the gross structure of a cyclic heptapeptide bearing an unprecedented pyrazolone ring connected to a d-arabinitol via an amide bond. The absolute configuration of <b>1</b> was established by multistep chemical derivatizations, comprehensive NMR, and LC/MS analyses of the derivatives and quantum mechanics-based computational methods. WS9326H (<b>1</b>) displayed significant antiangiogenesis activity

Structural Revision of Baulamycin A and Structure–Activity Relationships of Baulamycin A Derivatives

Total synthesis of the proposed structure of baulamycin A was performed. The spectral properties of the synthetic compound differ from those reported for the natural product. On the basis of comprehensive NMR study, we proposed two other possible structures for natural baulamycin A. Total syntheses of these two substances were performed, which enabled assignment of the correct structure of baulamycin A. Key features of the convergent and fully stereocontrolled route include Evans Aldol and Brown allylation reactions to construct the left fragment, a prolinol amide-derived alkylation/desymmetrization to install the methyl-substituted centers in the right fragment, and finally, a Carreira alkynylation to join both fragments. In addition, we have determined the inhibitory activities of novel baulamycin A derivatives against the enzyme SbnE. This SAR study provides useful insight into the design of novel SbnE inhibitors that overcome the drug resistance of pathogens, which cause life-threatening infections