Dehydrative cyclization Subject

Sydnones were the first mesoionic molecules subjected to detailed study, and are named after the University of Sydney where they were first prepared by Earl and Mackney in 1935. Sydnones are generally prepared by dehydrative cyclization of N-nitrosamino acids, which are synthesized by N nitrosation of amino acids [6]. Sydnone derivatives have been extensively studied for... 

A very short and elegant synthesis of the 16-rtiembered dilactone ( )-pyrenophorin (515) has been accomplished by the dipolar cycloaddition reaction of a trialkylsilyl nitronate (81TL735). Nitromethane was added to 3-buten-2-one and the carbonyl group of the product reduced with sodium borohydride. The nitro alcohol (511) was converted to the acrylate (512) which was then subjected to a dimerization-cyclization reaction by treatment with chlorotrimethylsilane and triethylamine in dry benzene. Hydrogenation of the mixture of isoxazoline products (513) over palladium on charcoal followed by double dehydration of the intermediate bis-/3-hydroxyketone (514) led to ( )- and meso-pyrenophorin (Scheme... 

An improved synthesis of the Cn-terpenic lactone Dihydroactinidiolide was described by A.K. Bose et al. [35]. The synthesis started from a commercially available aldehyde that was subjected to treatment with m-CPBA and a catalytic amount of PTSA (Scheme 10). The intermediate epoxy acid underwent cyclization resulting in the formation of Aeginetolide. Dehydration has been reported earlier by heating of this compound with aqueous NaOH, at 60 °C for 24 h, or with SOCI2 and pyridine at room temperature for 5 h. The authors observed expeditious and convenient dehydration of this compound supported on silica gel, under microwave irradiation for 5 -10 min (domestic oven), yielding Dihydroactinidiolide in 80% yield. 

There are a few examples of intramolecular alkylation and related processes involving N-1. Base-catalyzed cyclization of the appropriate 2-substituted thioacid derivatives have given (62) and (63). In addition cyclization of a series of ketones (64) gives the tertiary alcohols (65) which are subject to dehydration (Scheme 21) (74CRV279). 

The reaction of carbamoyl phosphate with aspartate to produce W-carbamo-ylaspartate is the committed step in pyrimidine biosynthesis. The compounds involved in reactions up to this point in the pathway can play other roles in metabolism after this point, A -carbamoylaspartate can be used only to produce pyrimidines—thus the term committed step. This reaction is catalyzed by aspartate transcarbamoylase, which we discussed in detail in Ghapter 7 as a prime example of an allosteric enzyme subject to feedback regulation. The next step, the conversion of A-carbamoylaspartate to dihydroorotate, takes place in a reaction that involves an intramolecular dehydration (loss of water) as well as cyclization. This reaction is catalyzed by dihydroorotase. Dihydroorotate is converted to orotate by dihydroorotate dehydrogenase, with the concomitant conversion of NAD to NADH. A pyrimidine nucleotide is now formed by the reaction of orotate with PRPP to give orotidine-5 -monophosphate (OMP), which is a reaction similar to the one that takes place in purine salvage (Section 23.8). Orotate phosphoribosyltransferase catalyzes this reaction. Finally, orotidine-5 -phosphate decarboxylase catalyzes the conversion of OMP to UMP... 

Regioselective techniques were developed to direct the cyclization of unsymmetrical esters. An interesting example of this aspect of the Dieckmann condensation is the synthesis of ip-methylcarbapenems by Tanabe and co-workers, ip-methylcarbapenems is a structure that exists in potent and broad antibacterial compounds, such as meropenem and biapenem, which renders it synthetically interesting for the synthesis of some close analogues 30a-d. Thioesters 29 was subjected to cyclization under dehydration type Ti-Dieckmann condensation conditions 3.0 equivalents of the TiCU and 3.3 equivalents of the base BusN were used to give the vinyl... 

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