Succinimide derivatives

The succinimide derivative (234) can be used in peptide synthesis for conversion of amino acids into their succinimide esters (235 Scheme 41) (79CL1265). 3-Substituted mercapto-1,2-benzisothiazole 1,1-dioxides (236) have been recommended as an odourless means of storage of thiols. The latter are readily regenerated by the action of piperidine (81CL1457). 

Teoc-O-succinimidyl, NaHC03 or TEA, dioxane, H2O, rt, overnight, 43-96% yield.The use of Teoc-OSu for the protection of amino acids proceeds without oligopeptide formation. Teoc-O-benzotriazolyl was also examined, but was inferior to the succinimide derivative. Teoc-OC6H4-4-N02, NaOH, r-BuOH, 66-89% yield. - ... 

In a more recent study on 1,3-dipolar cycloaddition reactions the use of succi-nimide instead of the oxazolidinone auxiliary was introduced (Scheme 6.19) [58]. The succinimide derivatives 24a,b are more reactive towards the 1,3-dipolar cycloaddition reaction with nitrone la and the reaction proceeds in the absence of a catalyst. In the presence of TiCl2-TADDOLate catalyst 23a (5 mol%) the reaction of la with 24a proceeds at -20 to -10 °C, and after conversion of the unstable succinimide adduct into the amide derivative, the corresponding product 25 was obtained in an endojexo ratio of <5 >95. Additionally, the enantioselectivity of the reaction of 72% ee is also an improvement compared to the analogous reaction of the oxazolidinone derivative 19. Similar improvements were obtained in reactions of other related nitrones with 24a and b. 

Label amino function in DNA probe with N-hydroxy succinimide derivatives of acridinium esters. 

Considering now glutarimide derivatives, we find that 2-phenylglutari-mide (4.196, R=H) was not a substrate for the partially purified rat liver DHPase, in contrast to glutarimide itself [114][123], Thus, here, the introduction of the Ph group had the opposite effect than in succinimide derivatives. Similarly, no ring-opened metabolite of glutethimide (4.196, R=Et) was found either in vitro or in vivo [124],... 

Figure 13.11. Formation and hydrolysis of succinimides derived from aspartic acid. Table 13.20. Preparation of imides and related compounds.

Li and coworkers have previously found that in the presence of an /V-hetero-cyclic carbene catalyst m-4-formyl-(3-lactams underwent the ring expansion reaction to afford succinimide derivatives [242]. More recently, they reported the kinetic resolution version of this transformation attempted with a chiral /V-heterocyclic carbene (Scheme 113), leading to m-4-formyl-(3-lactams with moderate ee of 64% [243]. 

On the other hand, several nucleophilic reagents and catalysts have been found capable of promoting the ring expansion of 4-formyl p-lactams, and/or their imine derivatives, to afford open chain acyl thiazole or succinimide derivatives. For example, treatment of 4-formyl p-lactam 199 with 2-(trimethylsilyl)thiazole,... 

Tetrabutylammonium cyanide catalyses ring expansion of 4-(arylimino)methyl-azetidin-2-ones to 5-aryliminopyrrolidin-2-ones through a novel N(l)-C(4) bond cleavage of the /3-lactam nucleus and provides for an efficient one-pot protocol to enantiopure succinimide derivatives (Scheme 20).36... 

Bodanszky, M. and Natarajan, S. (1975) Side reactions in peptide-synthesis. 2. Formation of succinimide derivatives from aspartyl residues. /. Org. Chem. 40, 2495-2499. 

Ishizume K, Kojima A, Antoku F, Saji I, Yoshigi M. Succinimide derivatives. 

If the process which is being observed (generally by NMR spectroscopy) is nitrogen inversion, procedure 1 should increase markedly the inversion barrier, 2 and 3 should decrease it (the barrier should even disappear in succinimide derivatives). These procedures have been used for instance for distinguishing between nitrogen inversion and hindered rotation about the N—O, N—S and N—P bonds in hydroxylamines 112>, sulfenamides 57 113> and amino phosphines U4>. 

Scheme 24 Absolute asymmetric photocyclization of a succinimide derivative involving a 1,5-hydrogen shift.

Enholm [26] has reported the first examples of asymmetric radical cy-clizations on soluble polymer supports. The stereocontrol element employed consists of a (+)-isosorbide group attached by a 4-carbon chain to each subunit of a soluble succinimide-derived ROMP backbone. Treatment of the radical cychzation substrate 162 with tributyltin hydride in the presence of zinc chloride followed by hydrolysis of the resulting polymer-supported ester 163 gave the desired product 164 in 80% yield and > 90% ee (Scheme 38). The use of alternative Lewis acids, such as magnesium bromide etherate and ytterbiiun (III) triflate, resulted in lower enantioselectivities, 84% and 72% respectively. No such decrease in selectivity was observed in analogous reactions carried out off-support [27], suggesting that the polymer backbone is somehow responsible for this phenomenon. 

The stereoselective formation of /3-hydroxy selenides has also been reported 36 in the reaction of alkenes with, V-(phenylseleno)phthalimide or the succinimide derivative in aqueous acetonitrile or dichloromethane. The use of phenylselenenyl chloride under these conditions gives similar results (Table 5)37. 

SCHEME 33. Reaction of benzoxazine succinimide derivative with a vacant p-position... 

The reaction of succinimide derivatives wifh catalytic amounts of Al(OTf)3 proceeded via several stepwise reactions, resulting in ring-enlargement (Scheme 6.157) [201]. Both bond-breaking and bond-making were assumed to be readily promoted by the strong Lewis acidity of Al(OTf)3. These involve intramolecular rearrangement of fhe C-N bond consistent with attack at fhe central carbon atom of the allenyl intermediate. 

Obelin-biotin complex was successfully obtained using succinimide derivatives of biotin, with less than 30% of its bioluminescent activity lost under the synthesis conditions. The biotinylated obelin is a universal label, suitable for any immunoassay through the avidin bridge. As an example, Fig.l gives the scheme of a solid-phase microanalysis of alphafetoproteins in standard human sera and displays the results of this analysis. 

---