One-carbon homologation of geranyl and farnesyl chlorides to secondary JV-methylamines (12 and 17) via -lithioformamidine alkylations followed by N-alkylation with bromoacetate esters afforded a-(homogeranylamino)and a-(homofarnesylamino)acetates 13 and 18. After -famesylation of 13, hydride reductions gave branched and straight-chain tertiary /3-amino alcohols 15 and 19. The diphosphate derivatives (7 and 8) of 15 and 19 prepared by Sn2 displacements may be regarded as "aza analogs" of plausible carbocation intermediates (5 and 6) in the biosynthesis of squalene and geranylgeranyl diphosphate since, in preliminary collaborative evaluations, they inhibit the respective synthase enzymes at micromolar concentrations.Farnesyl diphosphate (FPP, 1) is situated at an important branch point in the isoprenoid biosynthetic pathway (Scheme I).1-2 3Reductive head-to-head coupling of two molecules of FPP via presqualene diphosphate (2) leads to squalene (3), the precursor of triterpenes and sterols. Chain elongation by alkylation of FPP with isopentenyl diphosphate (IPP) produces geranylgeranyl diphosphate (GGPP, 4), which is an intermediate in the biosynthesis of cyclic diterpenes, carotenoids, dolichol, ubiquinones, phytyl derivatives, and the recently discov-compounds 7,8,14a, 23, and 24 (7 pages). Ordering information is given on any current masthead page.
Poly(dipeptamidininm) Salts: Definition and Methods of PreparationPoly(dipeptamidines) are polypeptide derivatives in which the carbonyl oxygen of each second backbone amide group is replaced by an imine nitrogen (see A). So far, such derivatives have been unknown. Polyprotonated salts of them ( = poly(dipeptamidinium) salts) are of interest in view of their intrinsic constitutional relationship to the structure of polynucleotides: the number of covalent bonds between neighboring centers of positive charge in poly(dipeptamidinium) salts is identical to the number of covalent bonds between neighboring centers of negative charge in natural polynucleotides (see D). Poly(dipeptamidinium) polycations and polynucleotide polyanions are constitutionally and electrostatically complementary structures. Since poly(dipeptamidines) are (formally) polymers of dipeptide nitriles, and, since they can be expected to give polypeptides on hydrolysis, the relationship mentioned above deserves attention and experimental study in context with the problem of designing chemical models of biogenesis.This paper describes methods for the chemical preparation, the spectral characterization, and some chemical properties of homodipeptidic pol y(dipeptamidinium) salts in the L-alanyl-glycyl and L-phenylalanyl-glycyl series.The methods of preparation include a stepwise construction of defined lower oligomers (up to hexamer) as well as, in the ~-alanyl-glycyl series, a one-operation poly-condensation procedure leading to polymers containing an average of ca. 20 dipeptamidinium units (Schemes 4,6 and 7).Als Poly (dipeptamidine) bezeichnen wir Polypeptid-Derivate, in welchen der Carbonyl-Sauerstoff jeder zweiten peptidischen Amid-Gruppe durch einen Imin-Stickstoff ersetzt ist (vgl. A). Solche Verbindungen sind formal Polymere von Dipeptid-nitnlen B.
Substituted alpha-(phenylhydrazono)phenylacetonitrile derivatives have been discovered which constitute a series of potent uncouplers of oxidative phosphorylation. Systematic variation of substituents on both benzene rings has clearly demonstrated the importance of steric congestion around the ionisation site and delocalisation of negative charge in the anionic form. Replacement of the cyano group by other electron-withdrawing groups leads to a dramatic decrease in uncoupling activity. The sub-nanomolar levels of uncoupling activity found in certain members indicate that these compounds are the most potent uncouplers yet reported.
The search for new active molecules with novel modes of action and desirable physical properties is an ongoing endeavour. This publication describes the follow-up chemistry of a biological hit discovered in the screening system of Novartis Crop Protection, the legacy agrochemical parent
of Syngenta Crop Protection. This chemistry was optimized through classical synthetic methods and automated parallel synthesis with coverage of important physical properties such as lipophilicity or Clog P and solubility. Preliminary biological activity from the greenhouse and field data with
symptomology is presented.
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