Gideon Shapiro

Synthesis of both D- and L-Fmoc-Abu[PO(OCH2CHCH2)2]-OH for solid phase phosphonopeptide synthesis

Abstract The Schollkopf bislactim ether asymmetric amino acid synthesis was coupled with a subsequent enzyme mediated ester hydrolysis to generate a practical synthesis of both D and L enantiomers of Fmoc-Abu[PO(OCH2CHCH2)2]-OH (6). With this building block phosphonopeptide isosteres of serine phosphopeptides are accessible by Fmoc-solid phase peptide synthesis.

Mild and rapid azide- mediated, palladium catalyzed cleavage of allylester based protecting groups

Abstract Under palladium catalysis various allylester protecting groups are rapidly cleaved in high yield with the reagent 8:3 trimethylsilylazide/tetrabutylammonium fluoride. The efficiency of this method makes it particularly useful for solid phase deprotections.

Asymmetric synthesis of a protected phosphonate isostere of phosphothreonine for solid-phase peptide synthesis

Abstract The first enantiospecific synthesis of 2 , a phosphonate isostere of phosphothreonine suitably protected for solid-phase peptide synthesis, has been achieved by coupling the highly face-selective conjugate addition of the lithium salt of Schollkopfs bislactim ether to E -prop-2-enyl-phosphonates with a selective enzymatic carboxylic ester hydrolysis. The absolute configuration of the products has been assigned from the X-ray structure of the adduct 9c .

Enantiospecific synthesis of 2-amino-3-methyl-4-phosphonobutanoic acids via 14-addition of lithiated Schöllkopf anion to prop-2-enylphosphonates

Abstract High diastereoselectivity in the conjugate addition of lithiated Schollkopfs bislactim ethers to E - and Z - prop-2-enylphosphonates was utilized to achieve a direct asymmetric synthesis of all four diastereoisomers of 2-amino-3-methyl-4-phosphonobutanoic acid, i.e. (+)-(2 S , 3 R )- 4a , (+)-(2 S , 3 S )- 4b and their corresponding enantiomers. Their relative configuration was definitively assigned from an NMR study of oxaphosphinane derivatives of both diastereoisomers.

Fmoc solid phase synthesis of serine phosphopeptides via selective protection of serine and on resin phosphorylation

Abstract An Fmoc based solid phase method for the synthesis of phosphoserine peptides has been developed which is amenable to standard protocols on automated synthesizers. The serine residue to be phosphorylated is protected with a t-butyldimethylsilyl group which is selectively removed from the resin bound protected peptide. On resin phosphorylation and final deprotection/cleavage are performed in standard fashion to yield serine phosphopeptides of significant length and complexity.

Asymmetric synthesis of (+)-pilosinine: a formal synthesis of (+)-pilocarpine

Abstract An efficient asymmetric synthesis of enantiomerically pure (+)-pilosinine achieved in 6 steps from a known chiral bromoacyloxazolidinone.

Combined Fmoc-Alloc strategy for a general SPPS of phosphoserine peptides; preparation of phosphorylation-dependent tau antisera

A block method for the solid phase synthesis (SPPS) of serine phosphopeptides has been developed using a combination of Fmoc and Alloc strategies. Alloc-Ser[PO(OCH2CH CH2)2] OH2, prepared in a one pot procedure from Alloc-Ser-OH, was introduced at the N-terminus of a sequence prepared by standard Fmoc-SPPS. Global cleavage of the allyl ester based protecting groups, followed by coupling of a tripeptide fragment, led to the tau phosphopeptide, 1. Using tau phosphopeptides a series of phosphorylation state-dependent antisera to human tau protein have been raised. These antisera are valuable tools for studying the tau protein which is found in an abnormal, hyperphosphorylated form in Alzheimers disease brain.

Solid phase synthesis of phosphonoserine isosteres of phosphoserine peptides

Abstract Using the recently synthesized building block L-Fmoc-Abu[PO(OCH2-CHCH2)2]-OH, (5) phosphonopeptide isosteres of serine phosphopeptides are readily accessible by Fmoc-solid phase peptide synthesis.

Synthesis of enantiomerically pure muscarine analogs

Abstract An efficient EPC-synthesis of muscarine and muscarone analogs has been devised with 2,S-ethyl lactate as the chiral starting material from which the key intermediate, phosphonate 5, was derived. The piperidine muscarine analog 3, (2S,3R)-1-oxa-2,8-dimethyl-3-oxo-8-azaspiro[4.5]decane, was prepared from 5 in seven steps in 22% overall yield.

Stereochemistry of intramolecular [2+2] photocycloadditions of 4-(4,5-hexadienyl)-2-cyclohexen-1-ones

Abstract Intramolecular [2+2] photocycloaddition of 4-(allenic-substituted)-2-cyclohexen-1-ones has been shown to be sensitive to change in substitution pattern and the nature of the reacting unsaturates. Initial bonding at C-2 of the enone is indicated.