The Paradox of Antimalarial Terpenoid Isonitrile Biosynthesis Explained. Proposal of Cyanoformate as an NC Delivery Vector.

Marine sponge diterpenoid isonitriles are exceptional nitrogenous natural products that exhibit antiplasmodial activity. Their biosynthesis presents a biosynthetic puzzle: how do the elements of NC engage terpenyl carbocations in isoprenoid secondary metabolism, and what is the biosynthetic precursor of the NC group? Cyanoformic acid (NC-COOH, ) is proposed as a plausible delivery vehicle of NC that resolves a paradox in the commonly held proposition that an inorganic cyanide anion, CN, terminates terpenoid isonitrile (TI) biosynthesis. DFT calculations of NC-COOH and its conjugate base, cyanoformate, NC-COO (), support high nucleophilicity at N and explain bond-forming constitutionality: attack at N and formation of an isonitrile over its nitrile isomer.

Empirical Chiroptical Analyses of Vicinal Bromochloro Natural Products by van't Hoff's Principle of Optical Superposition: Assignment of the C-16 Configurations of Callophycols A and B.

A simple empirical method is described that allows the assignment of absolute configurations of natural products containing chiral vicinal bromochloro (VBC) units, including the bromochloro substituted isoprenyl units present in the structures of antiproliferative halomon () and its halogen-swapped isomer -halomon () from the red alga, , and callophycols A () and B () from . The relative configurations of and , published in 2007, were incomplete: C-16 was left unassigned. It is now shown that the additivity of molar rotations, [] (herein, abbreviated [])─a consequence of van't Hoff's principle of optical superposition─could be used to deconvolute rotatory contributions, designated as [] and [] of the two remotely spaced chiral substructures within and using simple arithmetic.

Small molecule in situ resin capture provides a compound first approach to natural product discovery.

Culture-based microbial natural product discovery strategies fail to realize the extraordinary biosynthetic potential detected across earth's microbiomes. Here we introduce Small Molecule In situ Resin Capture (SMIRC), a culture-independent method to obtain natural products directly from the environments in which they are produced. We use SMIRC to capture numerous compounds including two new carbon skeletons that were characterized using NMR and contain structural features that are, to the best of our knowledge, unprecedented among natural products.

Orthogonal Deprotection Strategy of Fmoc Provides Improved Synthesis of Sensitive Peptides: Application to Z-Arg-Lys-AOMK.

Protecting groups (PGs) in peptide synthesis have inspired advanced design principles that incorporate "orthogonality" for selective C- and N-terminus and side-chain deprotections. The conventionally acid-stable 9-fluorenylmethoxycarbonyl (Fmoc) group is one of the most widely used N-protection groups in solid- and solution-phase synthesis. Despite the versatility of Fmoc, deprotection by the removal of the Fmoc group to unmask primary amines requires the use of a basic secondary amine nucleophile, but this stratagem poses challenges in sensitive molecules that bear reactive electrophilic groups.