Mrinmoy Saha

Bio: Mrinmoy Saha is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Michael reaction & Total synthesis. The author has an hindex of 6, co-authored 12 publications receiving 107 citations. Previous affiliations of Mrinmoy Saha include Oregon State University.

Enantioselective approach to quinolizidines: total synthesis of cermizine D and formal syntheses of senepodine G and cermizine C.

Abstract: The formal syntheses of C5-epi-senepodine G and C5-epi-cermizine C have been accomplished through a novel diastereoselective, intramolecular amide Michael addition process. The total synthesis of cermizine D has been achieved through use of an organocatalyzed, heteroatom Michael addition to access a common intermediate. Additional key steps of this sequence include a matched, diastereoselective alkylation with an iodomethylphenyl sulfide and sulfone-aldehyde coupling/reductive desulfurization sequence to combine the major subunits. The utility of a Hartwig-style C–N coupling has been explored on functionally dense coupling partners. Diastereoselective conjugate additions to α,β-unsaturated sulfones have been investigated, which provided the key sulfone intermediate in just six steps from commercially available starting materials. The formal syntheses of senepodine G and cermizine C have been accomplished through an intramolecular cyclization process of a N-Boc-protected piperidine sulfone.

Lycopodium Alkaloids: An Intramolecular Michael Reaction Approach

Abstract: The Lycopodium alkaloids possess a rich history that has captured the attention of synthetic chemists across the globe. This large family consists of over 250 known natural products with diverse structural features and noteworthy biological activity. Herein, we interweave the synthetic accomplishments by others in the field with our own unified strategy to accessing multiple subfamilies of the Lycopodium alkaloids. This discussion includes lycopodine, the C10-hydroxy Lycopodium alkaloids (10-hydroxylycopodine, deacetylpaniculine and paniculine), pelletierine, cermizine D, fastigiatine, himeradine A, clavolonine and 7-hydroxylycopodine. A unifying feature of much of the work discussed within this account is the use of intramolecular Michael additions to construct key ring systems within the Lycopodium alkaloids. Examples include the use of an intramolecular keto-sulfone Michael reaction and an intramolecular heteroatom Michael reaction. 1 General Background on Lycopodium Alkaloids 2 Development of a Strategy for Lycopodium Alkaloids 2.1 Generalized Strategy 2.2 Known Syntheses of C10-Functionalized Lycopodium Alkaloids 3 Quinolizidine-Type Alkaloids 3.1 Background 3.2 Development of the Heteroatom Michael Reaction 3.3 Synthesis of the Core Lycopodine Building Block: Pelletierine 3.4 Total Synthesis of Cermizine D 3.5 Synthesis of the Eastern Half of Himeradine A 4 Lycopodine-Type Alkaloids 4.1 Total Syntheses of Lycopodine 4.1.1 Earlier Racemic Syntheses 4.1.2 Approach Toward the Tricyclic Skeleton of Lycopodine: Intramolecular Mannich 4.1.3 Enantioselective Total Syntheses of Lycopodine 4.2 Total Syntheses of Clavolonine (8-Hydroxylycopodine) 4.3 Total Synthesis of 7-Hydroxylycopodine 4.4 Synthetic Route for 10-Hydroxy Lycopodium Alkaloids 4.4.1 Background 4.4.2 Total Syntheses 4.4.3 Impact of the C10-Stereochemistry 5 Conclusion

Chemical Features Important for Activity in a Class of Inhibitors Targeting the Wip1 Flap Subdomain.

Abstract: The wild-type p53 induced phosphatase 1, Wip1 (PP2Cδ), is a protein phosphatase 2C (PP2C) family serine/threonine phosphatase that negatively regulates the function of the tumor suppressor p53 and several of its positive regulators such as ATM, Chk1, Chk2, Mdm2, and p38 MAPK. Wip1 dephosphorylates and inactivates its protein targets, which are critical for cellular stress responses. Additionally, Wip1 is frequently amplified and overexpressed in several human cancer types. Because of its negative role in regulating the function of tumor suppressor proteins, Wip1 has been identified as a potential therapeutic target in various types of cancers. Based on a recently reported Wip1 inhibitor (G-1), we performed an extensive structure-activity relationship (SAR) analysis. This led us to interesting findings in SAR trends and to the discovery of new chemical analogues with good specificity and bioavailability.

Development of new methods in modern selective organic synthesis: preparation of functionalized molecules with atomic precision

Abstract: The challenges of the modern society and the growing demand of high-technology sectors of industrial production bring about a new phase in the development of organic synthesis. A cutting edge of modern synthetic methods is introduction of functional groups and more complex structural units into organic molecules with unprecedented control over the course of chemical transformation. Analysis of the state-of-the-art achievements in selective organic synthesis indicates the appearance of a new trend — the synthesis of organic molecules, biologically active compounds, pharmaceutical substances and smart materials with absolute selectivity. Most advanced approaches to organic synthesis anticipated in the near future can be defined as 'atomic precision' in chemical reactions. The present review considers selective methods of organic synthesis suitable for transformation of complex functionalized molecules under mild conditions. Selected key trends in the modern organic synthesis are considered including the preparation of organofluorine compounds, catalytic cross-coupling and oxidative cross-coupling reactions, atom-economic addition reactions, methathesis processes, oxidation and reduction reactions, synthesis of heterocyclic compounds, design of new homogeneous and heterogeneous catalytic systems, application of photocatalysis, scaling up synthetic procedures to industrial level and development of new approaches to investigation of mechanisms of catalytic reactions. The bibliography includes 840 references.

A general overview of the organocatalytic intramolecular aza-Michael reaction.

Abstract: The organocatalytic intramolecular aza-Michael reaction gives access to enantiomerically enriched nitrogen-containing heterocycles in a very simple manner. Enals, enones, conjugated esters and nitro olefins have been employed as Michael acceptors, while moderate nitrogen nucleophiles such as sulphonamides, carbamates and amides have been shown to be appropriate Michael donors in this type of reaction. Additionally, the process has been performed under both covalent and non-covalent catalysis, with diaryl prolinols, imidazolidinones, thioureas and chiral binol phosphoric acids being the most frequently used catalysts. The level of efficiency reached with this protocol is demonstrated by the implementation of numerous tandem processes, as well as the total synthesis of several natural products.

Cutting-Edge and Time-Honored Strategies for Stereoselective Construction of C-N Bonds in Total Synthesis.

Abstract: The main objective of this review is to provide a comprehensive survey of methods used for stereoselective construction of carbon–nitrogen bonds during the total synthesis of nitrogen-containing natural products that have appeared in the literature since 2000. The material is organized by specific reaction in order of decreasing number of applications in natural product synthesis. About 800 total syntheses of natural products with stereogenic carbon–nitrogen bonds described since 2000 have been reviewed.

Interactions between HIV-1nucleocapsid protein andviral DNA may haveimportant functions intheviral life cycle

Abstract: Inthevirion coreofretroviruses, thegenomic RNAis tightly associated withnucleocapsid (NC)protein molecules, forming thenucleocapsid structure. NC protein, ahighly basic protein withtwozincfingers, isindispensable forRNAdimerization, encapsidation andtheinitiation ofreverse transcription inavian, murine andhumanretroviruses. Hereweshowthat NC protein ofHIV-1 (NCp7) andNCp7mutants bindtoDNA fragments representing proviral DNA sequences, forming stable complexes. NCp7andNCp7mutants formhighmolecular weight complexes withlarge DNA fragments andshowcooperativity inbinding tothe DNAs.Itappears thattheconserved basicresidues, andnotthezincfingers, areimportant forcomplex formation. Inaddition, NCp7andseveral NCp7mutants protect DNAsfromnuclease digestion while theDNA endsappear tobepoorly protected. NCp7hasbeen foundtobindtostrong stopcDNA,theinitial product ofreverse transcription, andtopromote theannealing ofthis cDNAtoHIV-1 RNAcorresponding tothe3'end ofthegenome.Inaddition, NCp7slightly stimulates an invitro INcleavage assay. Theseresults indicate that theinteractions between NCp7andproviral DNAmay beimportant during provirus synthesis and/or prior to integration.

Enzymatic Kinetic Resolution of 2-Piperidineethanol for the Enantioselective Targeted and Diversity Oriented Synthesis.

Abstract: 2-Piperidineethanol (1) and its corresponding N-protected aldehyde (2) were used for the synthesis of several natural and synthetic compounds. The existence of a stereocenter at position 2 of the piperidine skeleton and the presence of an easily-functionalized group, such as the alcohol, set 1 as a valuable starting material for enantioselective synthesis. Herein, are presented both synthetic and enzymatic methods for the resolution of the racemic 1, as well as an overview of synthesized natural products starting from the enantiopure 1.