With Maleimides

The 1.3-diene system formed by cydization is useful for further modifications. typically Diels-Alder reactions. The 1,3-diene 51 reacts with maleimide to give 52[35], Similarly, the 1.3-diene 59 undergoes a Diels-Alder reaction, and this sequence was used for the syntheses of sterepolide (60 )[37] and mer-ulidial[38]. 

A typical maleimide resin is synthesized by the Michael addition of MDA and BMI (Fig. 4). If the stoichiometrically equal amounts of MDA and BMI are added into the reaction solvent under controlled temperature, linear, high molecular weight polyaminoimide (PAI) results. To obtain crosslinkable oligomer (pre-polymer) with maleimide end groups, a calculated 1.1-1.8 times an excess... 

The intermolecular version of the above described reaction has also been reported [92]. In the first example the reaction of a rhodium catalyst carbonyl ylide with maleimide was studied. However, only low enantioselectivities of up to 20% ee were obtained [92]. In a more recent report Hashimoto et al. were able to induce high enantioselectivities in the intermolecular carbonyl ylide reaction of the... 

Several syntheses of annulated uracils of biological value were recently reported. The key reaction was a microwave-assisted one-pot [4 -i- 2] cycloaddition of oxazino[4,5-d]-, pyrano-[2,3-d]-, pyrido[2,3-dj- and pyrimido[4,5-djpyrimidines, in the sohd state [134] and under solvent-free conditions [135]. The synthetic approach was based on the reaction of NJ -di-methyl-5-formylbarbituric acid 208 with maleimide in the sohd state for 5 min under microwave irradiation at 120 °C to give the pyrano[2,3-d]pyrimi-dine derivative 209 in 90% yield (Scheme 76). The reaction of 208 with phenyl isocyanate under microwave irradiation in the absence of solvent... 

Scheme 10.10 1,3-Dipolar cycloadditions of azomethine ylides with maleimides in the...

The aqueous Diels-Alder reaction has also been used for bioconjugate studies. A Diels-Alder reaction of diene oligonucleotides with maleimide dieneophiles was used to prepare oligonucleotide conjugates in aqueous media under mild conditions (Eq. 12.39).102 A Diels-Alder-type cycloaddition of an electronically matched pair of saccharide-linked conjugated dienes and a dienophile-equipped protein was the... 

Figure 19.21 The rate of reaction of cysteine with maleimide-activated BSA was determined using an Ellman s assay for remaining sulfhydryl groups after the reaction, according to Figure 19.20. Nearly all of the available maleimides are coupled with sulfhydryls within 2 hour.

Similarly, dialkylated succinimide (82) was obtained in the electrolysis of acid (80) with maleimide (81) (Scheme 29) [107]. 

A frequently used strategy to couple peptides to the surface of liposomes consists in the use hydrophobic/amphipathic anchors that are functionalized with maleimide or bromoacetyl groups, i.e., thiol-reactive functions, which give by reaction with HS-peptides very stable thioether linkages. These functions are conveniently introduced into hydrophobic anchors such as phospholipids, e.g., PE (9,10), the adjuvant PamsCAG (11) or cholesterol... 

The reactions of A-phenyl a-r-butyl nitrone (PEN) with maleimides, maleic anhydride, and diethyl maleate have been studied by EPR and two types of spin adduct detected. They arise from the reductive addition of PEN to the alkenes and the degradation product of DEN (2-methyl-2-nitropropane). The deuterium and muonium kinetic isotope effects for the addition of the hydrogen atom to a variety of alkenes have been determined experimentally and theoretically. ... 

Triphenylthieno[3,4-c]pyrazole (414) can be presented as a hybrid of dipolar-contributing azomethine imine ylide (415) or thiocarbonyl ylide canonical forms 416. Upon reacting this ylide with electron-poor olefins, it behaved like a thiocarbonyl ylide. Thus, with maleimide, a mixture of endo (419) and exo adducts (420) were obtained (74JA4276), which resulted from addition at the thiocarbonyl moiety. The reaction of 414 with dimethyl acetylenedicarboxylate gives the desulfurized indazole 418 in addition to the adduct 417 (Scheme 41). 

Wittig olefination of 2-nitro-Z-cinnamaldehyde (1300) with the phosphonium bromide 1301 led to the diene 1302. The Diels-Alder cycloaddition of 1302 with maleimide (1303), followed by dehydrogenation with DDQ, afforded the phthali-mide 1304. Double deoxygenation of 1304 with triphenylphosphine (PPhs) in collidine gave O-methylarcyiiaflavin B (1305). Finally, heating of 1305 with molten pyridine hydrochloride led to arcyriaflavin B (346) (759) (Scheme 5.215). 

Gaseous HCl adds to maleimide (134). Even more general are quantitative additions of HBr, which succeed with maleimide (134), maleic anhydride, fu-maric acid (28), and maleic acid [28]. 

Azomethine ylides containing a leaving group can also be produced by the standard tautomerization route (e.g., species 60 with a cyano group on the ylide carbon). These species (e.g., 60 [R =Ph, PhCO,PhCH=CH R = H,Ph]) reacted with maleimides and with fiimarate, maleate, and acrylate esters to give adducts 61, which readily eliminated hydrogen cyanide (33). 

The third major area of AB benzocyclobutene technology has dealt with the reaction of benzocyclobutene with maleimide to form a substantially linear... 

With maleimide the endo adduct (93) results at 25 °C, but the exo adduct (94) at 90 °C the endo adduct also yields the exo adduct on heating. Reaction of furan with maleic acid in water occurs slowly and the adducts readily revert thermally to the addends. As expected, the rate of formation of the endo adduct (95) is initially faster than that of the exo adduct (96), but after 10 days the ratio is 1 1 both isomers may be isolated (73T2491). Fumaric acid only adds in poor yield to furan under ordinary conditions, but this may be overcome by use of fumaryl chloride (79CC542). 

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