@article {48235, title = {Kupyaphores are zinc homeostatic metallophores required for colonization of Mycobacterium tuberculosis}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, year = {2022}, month = {FEB}, pages = {e2110293119}, type = {Article}, abstract = {

Mycobacterium tuberculosis (Mtb) endures a combination of metal scarcity and toxicity throughout the human infection cycle, contributing to complex clinical manifestations. Pathogens counteract this paradoxical dysmetallostasis by producing specialized metal trafficking systems. Capture of extracellular metal by siderophores is a widely accepted mode of iron acquisition, and Mtb iron-chelating siderophores, mycobactin, have been known since 1965. Currently, it is not known whether Mtb produces zinc scavenging molecules. Here, we characterize low-molecular-weight zinc-binding compounds secreted and imported by Mtb for zinc acquisition. These molecules, termed kupyaphores, are produced by a 10.8 kbp biosynthetic cluster and consists of a dipeptide core of ornithine and phenylalaninol, where amino groups are acylated with isonitrilecontaining fatty acyl chains. Kupyaphores are stringently regulated and support Mtb survival under both nutritional deprivation and intoxication conditions. A kupyaphore-deficient Mtb strain is unable to mobilize sufficient zinc and shows reduced fitness upon infection. We observed early induction of kupyaphores in Mtb-infected mice lungs after infection, and these metabolites disappeared after 2 wk. Furthermore, we identify an Mtb-encoded isonitrile hydratase, which can possibly mediate intracellular zinc release through covalent modification of the isonitrile group of kupyaphores. Mtb clinical strains also produce kupyaphores during early passages. Our study thus uncovers a previously unknown zinc acquisition strategy of Mtb that could modulate host-pathogen interactions and disease outcome.

}, keywords = {metallophore, nutritional immunity, tuberculosis, zinc}, issn = {0027-8424}, doi = {10.1073/pnas.2110293119}, author = {Mehdiratta, Kritee and Singh, Shubham and Sharma, Sachin and Bhosale, Rashmi S. and Choudhury, Rahul and Masal, Dattatraya P. and Manocha, Alzu and Dhamale, Bhushan Dilip and Khan, Naseem and Asokachandran, Vivekanand and Sharma, Pooja and Ikeh, Melanie and Brown, Amanda C. and Parish, Tanya and Ojha, Anil K. and Michael, Joy Sarojini and Faruq, Mohammed and Medigeshi, Guruprasad R. and Mohanty, Debasisa and Reddy, D. Srinivasa and Natarajan, Vivek T. and Kamat, Siddhesh S. and Gokhale, Rajesh S.} } @article {48143, title = {Ready access to densely substituted furans using Tsuji-Wacker type cyclization}, journal = {Journal of Organic Chemistry}, volume = {87}, year = {2022}, month = {JAN }, pages = {556-568}, type = {Article}, abstract = {

A competent method for the construction of highly substituted furans catalyzed by Pd(II) and Cu(II) chloride has been developed. The method provides easy access to di-, tri-, and tetrasubstituted furans from corresponding diols with relatively mild conditions in a unified strategy. The developed method has been successfully tested with more than 25 substrates, which resulted in furans of multiple substitution patterns with up to 84\% isolated yields.

}, issn = {0022-3263}, doi = {10.1021/acs.joc.1c02567}, author = {Masal, Dattatraya P. and Choudhury, Rahul and Singh, Aman and Reddy, D. Srinivasa} } @article {49425, title = {Gram-scale synthesis of ({\textpm})-tylophorine}, journal = {Synlett}, year = {2024}, month = {JUL }, type = {Letter; Early Access}, abstract = {

We report a practical scalable synthesis of the natural product (+/-)-tylophorine by using an operationally simple protecting-group-free route from readily accessible starting materials. Synthesis of a cyclic N-acetyl diester compound through cyclization, followed by two key steps (decarboxylation and a Clemmensen reduction), provides access to the target molecule.

}, keywords = {alkaloids, Clemmensen reduction, decarboxylation, gram-scale synthesis, tylophorine}, issn = {0936-5214}, doi = {10.1055/a-2351-4828}, author = {Masal, Dattatraya P. and Reddy, D. Srinivasa} }