Lactam precursor

Other approaches to (36) make use of (37, R = CH ) and reaction with a tributylstannyl allene (60) or 3-siloxypentadiene (61). A chemicoen2ymatic synthesis for both thienamycia (2) and 1 -methyl analogues starts from the chiral monoester (38), derived by enzymatic hydrolysis of the dimethyl ester, and proceeding by way of the P-lactam (39, R = H or CH ) (62,63). (3)-Methyl-3-hydroxy-2-methylpropanoate [80657-57-4] (40), C H qO, has also been used as starting material for (36) (64), whereas 1,3-dipolar cycloaddition of a chiral nitrone with a crotonate ester affords the oxa2ohdine (41) which again can be converted to a suitable P-lactam precursor (65). 

The preparation of nylon resins from lactam precursors involves ring opening, which is facihtated by a controlled amount of water in the reaction mixture. The salt complex condenses internally to produce the polyamide (57). The synthesis of nylon-6 [25038-54-4] from S-caprolactam is as follows ... 

The studies described above show that a quinone methide or its aza-analogue quinonimine methide incorporated as a latent electrophilic species into a cyclic lactone or lactam precursor can modify a second nucleophilic residue within the enzyme active site after formation of the acyl-enzyme. Very efficient suicide... 

The structural integrity of enzymes in aqueous solution is often compromised by the addition of small quantities of water-miscible organic solvents. However, there are numerous examples, particularly using extremophiles, where enzymes have been successfully employed in organic solvent-aqueous mixtures.A good example is the savinase-catalysed kinetic resolution of an activated racemic lactam precursor to abacavir in 1 1 THF/water (Scheme 1.39). The organic solvent is beneficial as it retards the rate of the unselective background hydrolysis. 

The potential of the method is best demonstrated when the ring opening is preceded by chemo- and stereoselective alkylation reactions. As Fig. 12 shows, two main types of alkylation events can be carried out on the designed (3-lactam precursor. Type 1 alkylation takes place at the C3 position of the (3-lactam ring, with entrance of the electrophile R group from the side opposite to the Ar group at C4. The second one (type 2) takes place at the exocyclic carbon directly bonded to the... 

Penicillin C (or V) Amidase (PGA, PVA) /1-Lactam Precursors, Semi-synthetic /1-Lactams... 

This transformation has been used to prepare, from iV-bis(trimethylsilyl)methyl (3-lactams, /V-vinyl (3-lactams precursors of N-H (3-lactams via ozonolysis 226,256 This constitutes a valuable deprotection of /V-bis(trimethylsilyl)methyl (3-lactams. For an alternate deprotection technique see Section VI.B.l 1. 

Sometimes the /3-lactam precursors are constructed using DCC in the protection of the carboxylic acid group by reacting it with benzylhydroxylamine. N-tosyllactams are obtained similarly using DCC and 4-pyrrolidinopyridine to effect ring closure. 

Other marine natural products with potent antitumour and antiviral activities, the eudistomins, continue to attract attention. As part of a new synthetic approach to the eudistomins, the stereoselective formation of the P-lactam fused oxathiazepine 110 has been reported <03SL738> C-N bond formation from 106 (via 105) was used to complete the seven-membered ring, and then this product 107 was converted into 110 via 108 and 109. Unfortunately, after ring opening the P-lactam in 110 and setting up the substituents for indole ring formation, this crucial indolisation was not successful. Other pathways are being explored but the P-lactam precursor concept is a clever one. 

Scheme 17 Oxime oxalate amides as fS-lactam precursors...

The Nicholas reaction was used to synthesize the p-lactam precursor of thienamycin in the laboratory of P.A. Jacobi and thereby accomplish its formal total synthesis. The necessary p-amino acid was prepared by the condensation of a boron enolate (derived from an acylated oxazolidinone) with the cobalt complex of an enantiopure propargylic ether. The resulting adduct was oxidized with ceric ammonium nitrate (CAN) to remove the cobalt protecting group from the triple bond, and the product was obtained with a 17 1 anti.syn selectivity and in good yield. 

Pummerer rearrangement. Sulfoxides are converted into a-siloxy sulfides, in which the new 0-C bond is anti to the original S-0 bond. Accordingly, the rearrangement of chiral sulfoxides is enantioselective. The method is applicable to synthesis of /3-lactam precursors. ... 

A [2]catenane 10, possessing two cyclic tetraamine macrocycles, was prepared (77%) by the borane reduction of the corresponding / w-tetralactam VTNMR studies of 10 indicate that it is rather mobile and quite free to rotate, unlike that of the lactam precursor <97CL881>. 

Cydohexylidene-protected glyceraldehyde imines were used by Annunzi-ata et al. [54,55] for the synthesis of a 6-lactam precursor of thrombin and tryptase inhibitors [54], as well as for the inhibitor of serine protease [55]. 

A highly strained representative (173) of this class has been claimed to show bactericidal properties [92]. The four-membered fused ring was built by an intramolecular carbene insertion into the N-H bond of the y-lactam precursor 170 (Scheme 50). 

Chlorination of Activated Methylene Groups. Triflyl chloride was used for the high yielding chlorination of carbon acids, and this reaction was applied to the synthesis of simple 2,2-disubstituted heterocycles. This method has been extended to the preparation of heterocycles fused with -lactams. Treatment of a hydroxyphenylazetidinone with triflyl chloride and triethy-lamine afforded a hemiaminal in 90% yield, through the chlorination of the dibenzyl malonate moiety (eq 11). Performing the same transformation on a mercapto- -lactam precursor led to the formation of a sulfenyl chloride intermediate rather than to chlorination of the malonate moiety. ... 

Some final HR applications that use LTA are the preparation of Boc-protected 2-amino-3-fluoroquinoline 137 ° and 12-oxotetradecano-14-lactam precursor 139. " The late stages of a synthesis of epibatidine (140 141) employ LTA." ... 

There are several different ways in which a lactam precursor can be generated. An interesting but relatively specific synthesis is shown in reaction 8 and employs thiophene derivatives. Catalytic hydrogenation of bicyclic thiophene 2.69 gave 2-elhylhexahydroazepine-2-one [2.70) and acid hydrolysis gave 2-ethyl-7-amino-hexanoic acid, 2.77.33... 

Sliwa A, Marchand-Brynaert J, Luhmer M. DOSY-NMR analysis of ring-closing metathesis (RCM) products from 3-lactam precursors. Magn Reson Chem. 2011 49(12) 812-815. 

Scheme 4.58 Diastereoselective hydroformylation of a vinyl-p-lactam precursor.

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