This research proposal reflects our interest in the areas of new reaction methodology development, applications to the synthesis of biologically active natural products, and their mechanism of action. We intend to develop and further refine synthetic methodologies for the synthesis of bioactive enamides, as well as related N-acylheminal natural products. We plan to study the chemical reactivity and biological activity of these molecules via specific biological collaborations. In addition to methodology development, the synthesis of structurally complex and biologically active natural products will be pursued: We intend to complete the synthesis of the salicylate macrolide lobatamide C in order to assign the absolute stereochemistry at unknown stereogenic centers, evaluate the biological activity of synthetic intermediates, and prepare both stereochemical analogues and photoaffinity probes. We intend to synthesize the cytotoxic peptide enamide natural products chondriamide C and terpeptin and diverse analogues using chemical modification of C-terminal peptides. We intend to pursue the asymmetric synthesis of novel antitumor and cell-cycle inhibitory macrolide oximidine I. We will pursue the asymmetric synthesis of the antitumor compound zampanolide whose natural resource has been depleted.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Medicinal Chemistry Study Section (MCHA)
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Schwab, John M
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Boston University
Schools of Arts and Sciences
United States
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Qi, Ji; Porco Jr, John A (2007) Rapid access to polyprenylated phloroglucinols via alkylative dearomatization-annulation: total synthesis of (+/-)-clusianone(1). J Am Chem Soc 129:12682-3
Porco Jr, John A; Su, Shun; Lei, Xiaoguang et al. (2006) Total synthesis and structure assignment of (+)-hexacyclinol. Angew Chem Int Ed Engl 45:5790-2
Zhang, Chen-Yu; Parton, Laura E; Ye, Chian Ping et al. (2006) Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucose-induced beta cell dysfunction in isolated pancreatic islets. Cell Metab 3:417-27
Lei, Xiaoguang; Porco Jr, John A (2006) Total synthesis of the diazobenzofluorene antibiotic (-)-kinamycin C1. J Am Chem Soc 128:14790-1
Han, Chong; Lee, Jonathan P; Lobkovsky, Emil et al. (2005) Catalytic ester-amide exchange using group (IV) metal alkoxide-activator complexes. J Am Chem Soc 127:10039-44
Shen, Ruichao; Inoue, Takao; Forgac, Michael et al. (2005) Synthesis of photoactivatable acyclic analogues of the lobatamides. J Org Chem 70:3686-92
Wang, Xiang; Porco Jr, John A (2005) Synthesis of the tetracyclic core of the tetrapetalones through transannular oxidative [4+3] cyclization. Angew Chem Int Ed Engl 44:3067-71
Wang, Xiang; Bowman, Emma Jean; Bowman, Barry J et al. (2004) Total synthesis of the salicylate enamide macrolide oximidine III: application of relay ring-closing metathesis. Angew Chem Int Ed Engl 43:3601-5
Han, Chong; Shen, Ruichao; Su, Shun et al. (2004) Copper-mediated synthesis of N-acyl vinylogous carbamic acids and derivatives: synthesis of the antibiotic CJ-15,801. Org Lett 6:27-30
Shen, Ruichao; Lin, Cheng Ting; Bowman, Emma Jean et al. (2003) Lobatamide C: total synthesis, stereochemical assignment, preparation of simplified analogues, and V-ATPase inhibition studies. J Am Chem Soc 125:7889-901

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