Subject(s)
Complement C5a/metabolism , Depsipeptides/pharmacology , GTP-Binding Proteins/metabolism , Mast Cells/drug effects , Muscle, Smooth/drug effects , Peptides/pharmacology , Animals , Depsipeptides/chemistry , Guinea Pigs , Humans , Mast Cells/metabolism , Molecular Structure , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscle, Smooth/physiology , Peptides/chemistry , RatsABSTRACT
[reaction--see text] An 18-step asymmetric synthesis of the bryostatin 1 "southern hemisphere" fragment (1) has been developed. Key steps include an aldol reaction between 6 and 7 and a dehydration to establish the (E)-exocyclic alkene in 2 and a stereoselective Luche reduction and protection with TESOTf to access 1.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Antibiotics, Antineoplastic/chemical synthesis , Lactones/chemical synthesis , Bryostatins , Indicators and Reagents , Macrolides , Magnetic Resonance Spectroscopy , StereoisomerismABSTRACT
[reaction: see text]. An efficient [2 + 2 + 2]-fragment condensation strategy is described for obtaining the cyclodepsipeptide core of verucopeptin. The 19-membered macrocycle was established through a Carpino HATU mediated macrolactamization, which proceeded in good yield under high-dilution conditions.
Subject(s)
Antibiotics, Antineoplastic/chemical synthesis , Depsipeptides , Peptides, Cyclic/chemical synthesis , Antibiotics, Antineoplastic/chemistry , Peptides/chemistry , Peptides, Cyclic/chemistryABSTRACT
A completely stereocontrolled asymmetric synthesis of an advanced B-ring synthon for the bryostatin family of antitumor agents is reported. Noteworthy features of our synthesis include the Smith-Tietze bis-alkylation reaction between 12 and 13 en route to C(2)-symmetrical ketone 10 and the totally stereoselective conversion of 10 into triol 18 via a Grignard addition tactic. Triol 18 was converted to epoxide 3 in nine steps, and an acid-catalyzed intramolecular Williamson etherification reaction completed the synthesis of 2.