Subject(s)
Alkenes/chemistry , Cyclohexanes/chemistry , Hydrazines/chemistry , Catalysis , Cyclization , StereoisomerismABSTRACT
[structure: see text] A synthesis of the C(1)-C(25) fragment of amphidinol 3 is described. The synthesis features two applications of double allylboration reaction methodology for the highly stereoselective synthesis of 1,5-diol units in the C(1)-C(15) segment.
Subject(s)
Alcohols/chemical synthesis , Alkenes/chemical synthesis , Boron Compounds/chemistry , Pyrans/chemical synthesis , Animals , Catalysis , Dinoflagellida/chemistry , StereoisomerismABSTRACT
[reaction: see text] A synthesis of the C(43)-C(67) fragment of amphidinol 3 (AM3) has been accomplished by a route that features the use of a double allylboration reaction for synthesis of 1,5-diol 4b, which serves as a precursor to dihydropyran 11.
Subject(s)
Alcohols/chemical synthesis , Alkenes/chemical synthesis , Boron Compounds/chemistry , Pyrans/chemical synthesis , Alkenes/chemistry , Animals , Catalysis , Dinoflagellida/chemistry , Molecular Structure , Pyrans/chemistry , StereoisomerismABSTRACT
Certain (Z)-1,5-syn-diols 2 may be converted into 2,6-trans-5,6-dihydropyrans by using phosphonium salt 4 or phosphorane 5 as dehydrating agents. A more general four step procedure converts the (Z)-1,5-syn-endiols into enantiomeric dihydropyrans ent-3 via regioselective silylation of the allylic alcohol unit followed by mesylate formation and base-promoted nucleophilic displacement.
ABSTRACT
A new 1-hydrazinodiene (1) has been developed and utilized in Lewis acid catalyzed, intermolecular Diels-Alder reactions with various electron-deficient alkenes. The hydrazine can then be deprotected, and a molecule of methanesulfinic acid is eliminated to provide a putative diazene intermediate (4), which then spontaneously undergoes a suprafacial 1,5-sigmatropic shift to yield stereochemically complex cyclohexenes. This method has been applied to the synthesis of a constitutionally and stereochemically complex decalin derivative.
Subject(s)
Alkenes/chemistry , Hydrazines/chemistry , Alkenes/chemical synthesis , Chemistry, Organic/methods , Cyclization , Hydrazines/chemical synthesisABSTRACT
Highly diastereo- and enantioselective syntheses of 1,5-disubstituted (E)-1,5-anti-pent-2-endiols 1 and (Z)-1,5-syn-pent-2-endiols 2 have been achieved via the one-pot coupling of two different aldehydes with either (E)-gamma-(1,3,2-dioxaborinanyl)-allyl]diisopinocampheylborane (4) or (E)-gamma-(4,4,5,5-tetraphenyl-1,3,2-dioxaborolanyl)allyl]diisopinocampheylborane (11), respectively. The indicated diols 1 and 2 are obtained in 63-95% yield with 89-96% ee and >/=20:1 diastereoselectivity in all cases. The bifunctional gamma-boryl-substituted allylborane reagents 4 and 11 were generated in situ by the hydroboration of allenes 3 and 10 with diisopinocampheylborane. The keys to the success of this method are the excellent stereocontrol in the allylboration step leading to 5 and the corresponding substituted methallylboronate derived from 11, the stereospecificity of the subsequent allylboration reaction of the substituted methallylboronate intermediates, and the ability of the diol auxiliary to induce equatorial or axial placement of the substituent alpha to boron in transition states 7 and 8.
Subject(s)
Alcohols/chemical synthesis , Allyl Compounds/chemical synthesis , Boranes/chemistry , Aldehydes/chemistry , Allyl Compounds/chemistry , StereoisomerismABSTRACT
Several classes of peptidomimetics of the efflux pump inhibitor D-ornithine-D-homophenylalanine-3-aminoquinoline (MC-02,595) have been prepared and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin in Pseudomonas aeruginosa. A number of the new analogues were as active or more active than the lead, demonstrating that a peptide backbone is not essential for activity.
Subject(s)
Anti-Infective Agents/pharmacology , Levofloxacin , Membrane Transport Modulators , Membrane Transport Proteins/antagonists & inhibitors , Ofloxacin/pharmacology , Peptide Fragments/chemical synthesis , Peptide Fragments/pharmacology , Pseudomonas aeruginosa/drug effects , Biological Transport, Active/drug effects , Drug Synergism , Microbial Sensitivity Tests , Molecular Mimicry , Molecular Structure , Peptide Fragments/chemistry , Pseudomonas aeruginosa/physiology , Structure-Activity RelationshipABSTRACT
Conformational restriction of the ornithine residue of the efflux pump inhibitor D-ornithine-D-homophenylalanine-3-aminoquinoline (MC-02,595, 2) furnished bioisosteric proline derivatives that were less toxic in vivo and as active as the lead in potentiating the activity of the fluoroquinolone levofloxacin via the inhibition of efflux pumps in Pseudomonas aeruginosa.