P-Sultams

Zajac M, Peters R (2009) Catalytic asymmetric synthesis of P-Sultams as precursors for taurine derivatives. Chem Eur J 15 8204-8222... 

Zajac M, Peters R (2007) Catalytic asymmetric formation of P-Sultams. Org Lett 9 2007-2010... 

A stereoselective one-pot synthesis of substituted 1,2-thiazetidine 1,1-dioxides (P-sultams) 55 started from heterocyclic pentafluorophenyl (PFP) sulfonates <06OL5513>. 

A short review of heterobond cleavage and sequential reactions of 1,2-thiazetidinones (P-sultams) has appeared <99PS193>. The first data for optically active P-sultams 33 have been reported. The precursor of 33 was the sulfonamide 32 which was obtained by use of a chiral tricarbonyl(r 6-arene)chromium(0) complex <99T14089>. 

A review of combinatorial synthesis including P-sultams has appeared <98AJC875>. 

Sulfonyl chlorides possessing an a-hydrogen undergo elimination of hydrogen chloride when treated with bases to yield sulfenes. Like ketenes, sulfenes can undergo [2 + 2] cycloaddition to support-bound imines to yield p-sultams (Entry 5, Table 15.2). 

P-Sultams.1 Reaction of 1 with imines and a base (usually pyridine) in THF results in 4-carbomethoxy-l,2-thiazetidine 1,1-dioxides (2) in 20-93% yield. All products have the trans-orientation. The N-unsubstituted P-sultams can be obtained by use of phenylselenenylethyl as the R group. This R group can be replaced by hydrogen in 70-90% yield by selenoxide elimination to an enamide, which is then treated with I2 and Na2S03.2... 

Unlike 3-lactams, unsubstituted P-sultams can undergo selective monoalkylation at C4 or dialkylation at N2 and C4 when the dianion is treated with a large excess of the electrophile. 

Thiazetidine 1,1,-dioxides (P-sultams) 67 were directly synthesised from pentafluorophenyl (PFP) isoxazolidine-4-sulfonates 66 under mild reducing conditions [Mo(CO)6, MeCN, H2O, reflux]. The process is stereoselective and goes through N-O bond cleavage followed by intramolecular displacement of the PFP group by the amine <06OL5513>. 

Sultams may be prepared by cydisation of the appropriate aminosulfonic acids and derivatives the ring closure involves nitrogen-sulfur bond formation. The method can be applied to the synthesis of p-sultams, y-sultams and 8-sultams examples are the syntheses of (173) and (174) (Scheme 72). Modifications of the procedure include aminolysis of the corresponding sultones, and oxidation of... 

Sulfenes (see Chapter 7, p. 114) generated from sulfonyl chlorides by treatment with a tertiary amine may be used to prepare p-sultams. Thus, the sulfonyl chloride (184) may be converted to the sultam (185) via the sulfene (186) by reaction with an activated alkene (Scheme 77)... 

Pummerer reaction. 4-Arenesulfinyl-P-sultams undergo Pummerer reaction which also triggers ring opening and loss of sulfur dioxide. a-Amino acid thiol esters are obtained. ... 

Because of their structural similarity to the fi-lactams, the solid-phase synthesis of 3-sultams (1,2-thiazetidine-l,1-dioxides) is of relevance. However, in spite of their structural analogy to the fi-lactams, very little is known about the biological activity of P-sultams. Thus far, the P-sultams examined have shown disappointingly weak P-lactamase inhibition activity [49], although by using combinatorial technologies... 

The asymmetric synthesis of c -3,4-disubstituted P-sultams 65, based on the oxidation of 1,2-aminothiols with H2O2 and ammonium heptamolybdate has been achieved <05S1807>. Different transition-state structures for the reactions of P-lactams and their sulfonyl analogues P-sultams with serine P-lactamases have been reported <05JA17556>. It has been discovered that the 3-oxo-P-sultam 66 is unusual in that it inhibits elastase by acylation resulting from substitution at the carbonyl center, C-N fission, and expulsion of the sulfonamide <05JA8946>. 

Reductive cleavage. Pentafluorophenyl isoxazolidine-4-sulfonates are converted into a-hydroxymethyl-p-sultams on treatment with Mo(CO)6 in aqueous MeCN at 90°. Cyclization occurs after the N-O bond is cleaved. ... 

Keywords Azitidinone Penicillin Solid phase synthesis p-Lactam p-Sultam Contents... 

A novel base catalysed rearrangement of A-aUcyl 3-oxo-P-sultams (25) leads to... 

The chemistry of P-lactams, p-sultams and P-phospholactams has been compared and the potential of the last two as mechanism based inhibitors of bacterial and mammalian proteases... 

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