Total synthesis of Class II and Class III Galbulimima Alkaloids

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010Vita. Cataloged from PDF version of thesis.Includes bibliographical references.I. Total Synthesis of All Class III Galbulimima Alkaloids We describe the total synthesis of (+)- and (-)-galbulimima alkaloid 13, (-)-himgaline anad (-)-himbadine. The absolute stereochemistry of natural (-)-galbulimima alkaloid 13 is revised to 2S. Sequential use of catalytic cross-coupling and cross-metathesis reactions followed by an intramolecular Diels-Alder reaction provided the required trans-decalin AB-ring system and masked the Cl 6-carbonyl as an N-vinyl carbamate for late stage unveiling in the form of the necessary C16-enone. A vinyl-radical cyclization secured the C-ring while successful execution of our strategy for introduction of the CDE-ring system in complex galbulimima alkaloids provided the target pentacycle with complete diastereoselection. II. Total Synthesis of (-)-Himandrine We describe the first total synthesis of (-)-himandrine, a member of the class II galbulimima alkaloids. Noteworthy features of this chemistry include a diastereoselective Diels- Alder reaction in the rapid synthesis of the tricycle ABC-ring system in enantiomerically enriched form, the use of a formal [3+3] annulation strategy to secure the CDE-ring system with complete diastereoselection, and successful implementation of our biogenetically inspired oxidative spirocyclization of an advanced intermediate. The successful and direct late-stage formation of the F-ring in the hexacyclic core of himandrine drew on the power of biogenetic considerations and fully utilized the inherent chemistry of a plausible biosynthetic intermediate.by Meiliana Tjandra.Ph.D

YURIDIS ANALISA QUICK RESPONSE CODE SEBAGAI SISTEM PEMBAYARAN DITINJAU DARI PERATURAN BANK INDONESIA NOMOR 18/40/PBI/2016 TENTANG PENYELENGGARAAN PEMROSESAN TRANSAKSI PEMBAYARAN

Countries in the world including Indonesia are increasingly developing from various aspects ofculture, health, economy, and continue to improve increasingly sophisticated technology. Banksin the aspect of the nation's economy have an important role as financial institutions that caninfluence the economic activities of a nation and play an active role in the progress anddeterioration of a nation's economy. The Quick Response Code is the latest innovation in theIndonesian banking industry to facilitate customers in conducting transactions, namely byconducting transactions using QR Code (barcode). This feature makes it easy for customers tosimply scan (barcode) the sticker / receipt from the merchant. The author's method that I use isnormative juridical. The author discusses how the application of risk management and legalprotection for QR Code users. Although the service and Implementation Regulations for the QRCode have been used by customers, these regulations must be discussed again and reformulatedwith regard to the protection and accountability of users of the QR Code and clear sanctions inthe event of losses caused by fraudsters. Complaint efforts in the event of a loss to the QR Codeuser, can submit complaints to Bank Indonesia as long as they meet these requirementsNegara-negara di dunia termasuk Indonesia semakin hari semakin terus berkembang dariberbagai aspek kebudayaan, kesehatan, ekonomi, dan terus meningkatkan teknologi yangsemakin canggih. Bank dalam aspek perekonomian bangsa memiliki peran penting sebagailembaga keuangan yang dapat mempengaruhi kegiatan perekonomian suatu bangsa dan ikutberperan aktif dalam kemajuan maupun keterpurukan perekonomian suatu bangsa. QuickResponseCode inovasi terbaru pada industri perbankan Indonesia untuk mempermudah nasabahdalam melakukan transaksi yaitu dengan melakukan transaksi menggunakan QR Code(barcode). Fitur ini memudahkan nasabah hanya dengan menscan (barcode) pada stiker/strukdari merchant. Metode penulis yang penulis gunakan adalah yuridis normatif. Penulismembahas bagaimana penerapan manajemen risiko dan perlindungan hukum terhadappengguna QR Code. Meskipun layanan dan Peraturan Implementasi terhadap QR Code sudahdigunakan oleh nasabah namun peraturan tersebut harus di diskusikan kembali dan dirumuskanulang terkait perlindungan dan pertanggungjawaban terhadap pengguna QR Code serta sanksiyang jelas apabila mengalami kerugian yang disebabkan oleh fraudster. Upaya pengaduanapabila terjadi kerugian terhadap pengguna QR Code, dapat menyampaikan pengaduan kepadaBank Indonesia sepanjang memenuhi persyaratan tersebu

Chemoselective and Enantioselective Oxidation of Indoles Employing Aspartyl Peptide Catalysts

Catalytic enantioselective indole oxidation is a process of particular relevance to the chemistry of complex alkaloids, as it has been implicated in their biosynthesis. In the context of synthetic methodology, catalytic enantioselective indole oxidation allows a rapid and biomimetic entry into several classes of alkaloid natural products. Despite this potentially high utility in the total synthesis, reports of catalytic enantioselective indole oxidation remain sparse. Here we report a highly chemoselective catalytic system for the indole oxidation that delivers 3-hydroxy-indolenines with good chemical yields and moderate to high levels of enantio- and diastereoselectivity (up to 95:5 er and up to 92:8 dr). These results represent, to our knowledge, the most selective values yet reported in the literature for catalytic asymmetric indole oxidation. Furthermore, the utility of enantioenriched hydroxy-indolenines in stereospecific rearrangements is demonstrated.National Institutes of Health (U.S.) and National Institute of General Medical Sciences (U.S.) (grant no. GM096403)National Institutes of Health (U.S.) and National Institute of General Medical Sciences (U.S.) (grant no. GM089732)Amgen, Inc.DuPont (Firm

Application of Virtual Screening to the Identification of New LpxC Inhibitor Chemotypes, Oxazolidinone and Isoxazoline

This report summarizes the identification and synthesis of novel LpxC inhibitors aided by computational methods that leveraged numerous crystal structures. This effort led to the identification of oxazolidinone and isoxazoline inhibitors with potent in vitro activity against P. aeruginosa and other Gram-negative bacteria. Representative compound 13f demonstrated efficacy against P. aeruginosa in a mouse neutropenic thigh infection model. The antibacterial activity against K. pneumoniae could be potentiated by Gram-positive antibiotics rifampicin (RIF) and vancomycin (VAN) in both in vitro and in vivo models

Optimization of novel monobactams with activity against carbapenem-resistant Enterobacteriaceae - Identification of LYS228

Metallo-β-lactamases (MBLs), such as New Delhi metallo-β-lactamase (NDM-1) have spread world-wide and present a serious threat. Expression of MBLs confers resistance in Gram-negative bacteria to all classes of β-lactam antibiotics, with the exception of monobactams, which are intrinsically stable to MBLs. However, existing first generation monobactam drugs like aztreonam have limited clinical utility against MBL-expressing strains because they are impacted by serine β-lactamases (SBLs), which are often co-expressed in clinical isolates. Here, we optimized novel monobactams for stability against SBLs, which led to the identification of LYS228 (compound 31). LYS228 is potent in the presence of all classes of β-lactamases and shows potent activity against carbapenem-resistant isolates of Enterobacteriaceae (CRE)

Potent Nonimmunosuppressive Cyclophilin Inhibitors With Improved Pharmaceutical Properties and Decreased Transporter Inhibition

Nonimmunosuppressive cyclophilin inhibitors have demonstrated efficacy for the treatment of hepatitis C infection (HCV). However, alisporivir, cyclosporin A, and most other cyclosporins are potent inhibitors of OATP1B1, MRP2, MDR1, and other important drug transporters. Reduction of the side chain hydrophobicity of the P4 residue preserves cyclophilin binding and antiviral potency while decreasing transporter inhibition. Representative inhibitor <b>33</b> (NIM258) is a less potent transporter inhibitor relative to previously described cyclosporins, retains anti-HCV activity in cell culture, and has an acceptable pharmacokinetic profile in rats and dogs. An X-ray structure of <b>33</b> bound to rat cyclophilin D is reported