Stereocontrolled synthesis of (+)-negamycin from an acyclic homoallylamine by 1,3-asymmetric induction

Abstract

Since modifications of C(l), C(7), C(8), and C(12) are not involved in the conversion 1 -* 2 -» 3, these centers in 1 are fully defined. To determine the stereochemistry at C(9) through C(11), however, requires careful interpretation of the stereospecific chemical processes involved. Construction of molecular models indicates the stereochemical relationships between 1, 2, and 3. Due to the extremely hindered "back" face of C(8) to C(12) in these molecules, solvolysis and elimination must involve substituents on the "front" face. The allylic displacements (SN2') of epoxide 1 and of methoxy derivative 2 must involve the predicted syn orientation of displacing and leaving groups.11 The NMR spectra of 1-3 support this contention. As a consequence of this reasoning, the epoxide stereochemistry at C(11) was established as S.The structure of pseudopterolide12 represents a novel monocyclic skeleton related only in part to cubitene,13 a 12-membered ring with two isopropenyl groups oriented 1,3 instead of 1,7. While pseudopterolide can be dissected symmetrically into two geranyl units in two possible ways, perhaps suggesting a biogenesis involving dimerization, the prevalence of the 14-membered ring cembrenoids in marine soft corals suggests a mechanism involving ring contraction.Acknowledgment. Research at the Scripps Institution was supported by the National Science Foundation Oceanography Section, under Grant OCE 80-14167. Research at Cornell University was supported by the National Institutes of Health under Grant CA 24487. We thank Dr. Frederick M. Bayer, Smithsonian Institution, for identification of Pseudopterogorgia acerosa (Pallas). We express our appreciation to Professor Robert Jacobs for his collaboration in evaluating the pharmacological (8) Preliminary X-ray photographs of the urethane 3 showed orthorhombic symmetry and lattice constants of a = 12.470 (2) A, b = 24.001 (2), and c = 9.356 (3) A were determined by a least-squares fit of 15 moderate 28 values measured on a diffractometer. Systematic extinctions, crystal density, and the presence of chirality were uniquely accommodated by space group P2\2{2 with a unit of CjgHjgBrNOT-HjO forming the asymmetric unit. All unique diffraction maxima with 28 < 114°were collected on a four-circle diffractometer using graphite monochroma ted Cu Ka (1.541 78 A) radiation and a variable-speed 1° scan. Of the 2189 reflections surveyed, 2041 (93%) were judged observed (|F0| > 3tr(F")) after correction for Lorentz, polarization, and background effects. A phasing model was achieved by standard heavy-atom methods.9 Full-matrix least-squares refinements using anisotropic non-hydrogen atoms, isotropic, fixed hydrogens, and anomalous scattering corrections for bromine have converged to a current residual of 0.095 for the structure shown and 0.099 for the enantiomer.10 (9) All crystallographic calculations were performed on a Prime 400 computer operated by the Materials Science Center and the Department of Chemistry, Cornell University. The principal programs used were as follows...

Ultrasound assisted synthesis of 1-amino-3-ferrocenyl-3-oxoprop-1-enes

“…5,6 The ferrocene derivatives exhibit also an antiplasmodial, [7][8][9] antitumor, 10 and DNA cleaving 12 activities, have an antiproliferative effects on the MCF7 cell lines, 11 activity and have chemotherapeutic action on drugresistant cancer. 4,13 On the other hand, enaminones are important building blocks in the synthesis of many heterocyclic compounds 14 and many therapeutic: antitumor, 15 antimicrobial, [15][16][17] anticonvulsant, 18 antiinflammatory, 19 analgesic, 19 ulcerogenic agents. 20 Keeping in view the biological importance of enaminones, 18,21 we have recently reported 22 the synthesis of (Z)-3-adamantyl-1-aryl-prop/but-2-en-1-ones which were tested for anti-inflammatory and anticancer properties.…”

LiClO4 CATALYZED AZA-MICHAEL ADDITION OF SECONDARY AMINES TO α,β-UNSATURATED ESTERS UNDER A SOLVENT-FREE CONDITION

“…Aza-Michael reaction products such as β-amino esters/ketones/nitriles are useful synthons for the preparation of several nitrogen containing bioactive natural products [2], antibiotics [3], and chiral auxiliaries [4]. Because a large number of biologically active compounds contain β-aminoketone or ester moiety [5], the development of novel methodologies for the preparation of these compounds is an attractive area of research in synthetic organic chemistry.…”

Citric Acid Catalyzed Synthesis of Amidoalkyl Naphthols under Solvent-free Condition: An Eco-friendly Protocol

“…Compounds bearing 1, 3-amino oxygenated functional groups are ubiquitous to a variety of biologically important natural products and potent drugs including a number of nucleoside antibiotics and HIV protease inhibitors, such as ritonavir and lipinavir. [3] Aminoalkyl naphthols have attracted strong interest to their useful biological and pharmacological properties such as adrenoceptor blocking, antihypertensive, and Ca2+ channel blocking activities [4][5][6][7][8]. Amidoalkyl naphthols are also important synthetic building blocks and are used as precursors for the synthesis of 1-aminomethyl-2-naphthol derivatives, which exhibit important cardiovascular activity [9].…”