Integerrinecic acid

Integerrinecic acid (36), which occurs as the dilactone in the pyirolizidine alkaloid integerrimine (33 Scheme 9), was obtained from ketone (34). The observed regioselectivity in the oxidation leading to (35) presumably results from steric and dipolar effects. ... 

Platynecic (Probably senecic acid-f integerrinecic acid) Platyphylline 133-135 ... 

Integerrinecic Acid and Senecic Acid and Their Diastereoisomers (95,97)... 

Chart III. The structure and physical properties of senecic acid, integerrinecic acid and their diastereoisomers (755,150-1 1),... 

Hydrolysis and the elimination of ethanol gave the unsaturated keto acid, XCII, which by way of its cyanhydrin yielded a ( )-trans- c A identical with ( )-integerrinecic acid (see Chart III). 

The (— )-senecic acid was also obtained by Mattocks and Warren (161) from the hydrolysis of isosenecionine obtained from retrosine by oxidation with sodium metaperiodate and reaction of the resulting keto compound with methylmagnesium iodide. The (-)-senecic acid was converted to (—)-integerrinecic acid lactone. The oxidation of this (— )-senecic acid with lead tetraacetate gave a keto acid (2,4-DNP, mp 183°, [aJu —11.6°) enantiomeric with that from (- -)-senecic acid (see Chart III). 

Labeled integerrinecic acid has been synthesized in our laboratories (208) from senecic acid (CLXXIX) by oxidation to the keto acid. 

The reactions of dimethyl methylphosphonate and the corresponding carbanion in the gas phase have been investigated. The carbanion displays a similar range of reactions to those encountered in solution, including olefmation with carbonyl compounds. The effect on olefin stereochemistry of a variety of conditions in reactions of a-phosphono lactones (e.g. 129) with ethanal and propanal has been studied and the results applied in syntheses of integerrinecic acid and senecic acid lactones. Yet further minor modifications of the conditions for phosphonate-olefination reactions, involving the use of lithium hydroxide as the base, have been reported. ... 

Two six-membered necic acid lactones 46 (integerrinedc acid lactone) and 47 (senedc acid lactone) having an exo-a-methylene moiety were synthesized by Wiemer et al. [45] in the stereocontrolled Horner-Wittig condensation of the a-phosphonolactone 48 with acetaldehyde (Scheme 20). When KHMDS in acetonitrile was used as a base in this reaction, a 9 1 mixture of E and Z products was obtained from which the -isomer of integerrinecic acid lactone 46 was isolated in 77% yield. When K2C03/18-crown-6/toluene was employed in a parallel... 

Integerrinecic acid (Scheme 3.25), despite its small size, has branches and functional groups enough to practise meaningful retrosynthesis. The construction plan of three very similar syntheses [40, 41, 42] (sequence of bond formation (1), (2), (3)) shows that all cuts are made to create branches with the aid of the existent functionality. Work backwards (3) —> (2) — (1) to recognize by which reactions a synthesis can be reahzed. For a completely different approach, see reference [43]. 

Scheme 13.13 Last step in a proposed synthesis of integerrinecic acid...

In 1982, Drewes and Emslie first reported the reaction of ethyl acrylate with acetaldehyde in the presence of DABCO and successfully employed this adduct in the synthesis of integerrinecic acid (3) (Scheme 2.2). Soon after that, Hoffmann et al. developed an interesting reaction between methyl/tcrt-butyl acrylates 4 and various aldehydes rmder the catalytic influence of DABCO to provide the corresponding a-hydroxyalkyl acrylate adducts 5 and elegantly applied one of these adducts to synthesis of racemic mikanecic acid (6) (Scheme 2.3). Since then, a series of reports" have emerged and transformed the MBH reaction into a very useful and promising tool for the construction of carbon-carbon bonds in synthetic chemistry (Scheme 2.4). 

The reaction of allyl acetates, halides and sulfides derived from the MBH adducts with carbon nucleophiles has been well investigated. In fact, Drewes and co-workers first reported the utilization of the nucelophilic addition of a MBH adduct in the stereoselective synthesis of (2 )-integerrinecic acid, a natural product with a trisubstituted olefinic moiety." Subsequently, Drewes et a/ 34,40d,ii9 carried out stereo- and regioselective addition of carbon nucleophiles derived from ethyl acetoacetate, malonate and phenylacetylide derivatives to various MBH halides and MBH acetates. 

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