IV-Protecting

The Michael addition of nitromethane to vinylogons esters of iV-protected amino acids proceeds v/ith good yields and v/ith good diastereoselecdvity fEq. 4.135. ... 

A neat synthesis of 4-nitroindole depends on an acyladon-deacyladon sequence from 2-methyl-3-nitroaniline, as shown in Eq. 10.53. On the other hand, treatment of iV-protected indoles v/ith acetyl nitrate generated in sini at bw temperanire gives the correspondmg... 

To date most of the nitriles studied have been simple alkyl or aromatic derivatives with little other functionality. We recently attempted to extend the reaction to iV-protected a-aminonitriles, derived by dehydration of a-aminoacid amides (Path A, Scheme 25), but this proved unsatisfactory, and therefore we investigated an alternative diazocarbonyl based route in which the order of steps was reversed, i.e. a rhodium catalysed N-H insertion reaction on the amide followed by cyclodehydration to the oxazole (Path B, Scheme 25). 

Bode and co-workers have extended the synthetic ntility of homoenolates to the formation of enantiomerically enriched IV-protected y-butyrolactams 169 from saccharin-derived cyclic sulfonylimines 167. While racemic products have been prepared from a range of P-alkyl and P-aryl substitnted enals and substitnted imi-nes, only a single example of an asymmetric variant has been shown, affording the lactam prodnct 169 with good levels of enantioselectivity and diastereoselectivity (Scheme 12.36) [71], As noted in the racemic series (see Section 12.2.2), two mechanisms have been proposed for this type of transformation, either by addition of a homoenolate to the imine or via an ene-type mechanism. 

Mitchell, J.R., follow, D.J., Potter, W.Z. Gillette, J.R. and Brodie, B.B. (1973b). Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J. Pharmacol. Exp. Ther. 187, 211-217. 

It should be emphasized that benzyloxycarbonylimidazolium salts are effective agents for the direct mono-iV-protection of deoxynucleosides as their benzyloxycarbonyl derivatives. No over-acylation occurs. However, bis(ter/-butyldimethylsilyl)-deoxy-guanosine failed to react with this reagent.[189]... 

The basic requirements for the CBMS II are to reliably detect and identify with sufficient sensitivity and selectivity both CWA and BWA in point detection and reconnaissance missions, in order to be deployable in wheeled reconnaissance vehicles and be operable by nontechnical personnel wearing, at the extreme, MOPP IV protective gear. Contrary to the usual practice for a military detector system, the CBMS II does not have its own requirements document. Instead, the requirements and specifications for the CBMS II are based on the detector requirements of the host platforms in which it will be deployed. These requirements are described in terms of performance, as opposed to the usual practice of being enumerated in volumes of detailed specifications. As is usual for a complex multiyear program, the requirements changed over the course of the CBMS II program as the requirements for the host platforms evolved. 

Treatment of the iV-protected 4-chloro-2-pyridone 151 with sodium prolinate in hot DMSO gives a prolinylpyr-idone, which may then be cyclodehydrated by acetic anhydride to give the pyridopyrrolizinone 152 <1994TL6985> (Scheme 42). The acetoxy group in 152 forms the basis for further functional group transformations, as outlined in... 

Several methods for synthesizing IV-protected (usually with electron-withdrawing groups) 2-and 3-haloindoles have been developed and the resulting haloindoles are much less prone to decomposition than the unsubstituted compounds. Bromination of A/-(phenylsulfonyl)indole (3), which is readily available via lithiation [9, 10] or phase-transfer chemistry [11, 12], affords 3-bromo-l-(phenylsulfonyl)indole (4) in nearly quantitative yield [12],... 

A reductive intermolecular Heck heteroarylation (hydroheteroarylation) of A-protected azabicyclo[2,2,l]heptene 165 has been used to construct 7-azabicyclo[2.2.1]heptane 166 in moderate yield [131, 132]. An asymmetric version of such a transformation to provide enantiomerically-enriched iV-protected epibatidine has also been described [128, 133]. It was found that introduction of Noyori s BINAP ligand resulted in the best enantioselectivities with 72-81% ee and a 53% yield. By using either the (R)- or (S)-BINAP ligand, either enantiomer was easily accessible. 

NL Benoiton, Y Lee, B Liberek, R Steinauer, FMF Chen. High-performance liquid chromatography of epimeric IV-protected peptide acids and esters for assessing race-mization. Int J Pept Prot Res 31, 581, 1988. 

Amino acids (including underivatized and iV-protected a- and fi-amino acids, either proteinic and unusual) Peptides... 

The direct A -nitration of the amino groups of the hexahydrotriazine (23) is only possible due to the inherent low basicity of the methylenediamine functionality. The methylenediamine unit is present in many cyclic and bicyclic polyamines and these are potential precursors to energetic polynitramines. Unfortunately, this route to polynitramines is rarely possible because such polyamines are usually intrinsically unstable and will readily equilibrate to a lower energy, less strained system. For the same reason, polyamines containing the methylenediamine functionality are difficult to prepare and isolate, often rapidly decomposing in both aqueous and acidic solution. A far more common route involves the preparation of iV-protected versions of the polyamine followed by nitrolysis (Section 5.6). Even so, examples of heterocyclic methylenediamine iV-nitration exist. 

Fuji and Kawabata further demonstrated the utility of their catalyst by successfully achieving the KR of iV-protected cyclic cw-amino alcohols [113], Hence, by using 5 mol% of 4-PPY 29 in the presence of a stoichiometric amount of collidine in CHCI3 at room temperature, a variety of cyclic cw-amino alcohol derivatives were resolved with moderate to good selectivities = 10-21) (Table 6) [113],... 

Notably, the aminoalkylation reaction did not occur with iV-protected indoles revealing the crucial role of the free N-H group for the activation by the phosphoric acid. This prompted the authors to postulate the transition state model depicted in Fig. 6. 

Tryptophan DKPs have shown to be an attractive subclass of this reaction with many active compounds including tryprostatin B and fumitremorgin B (Fig. 8), which are potent inhibitors of mammahan cell progression at the G2/M transition. Rhoden et al. describes the synthesis of a library of trypophan containing DKPs [43]. In this reaction (Scheme 21) iV-protected tryptophan 124 with different combinations of amines 126, isocyanides 127, and aldehydes 125 were combined in methanol and heated. The reaction was heated either via reflux or by microwave though yield did not increase significantly, time was reduced by 50-fold when reaction was heated via microwave. These reactions proved to be fast, scalable, and allow for extensive variation. 

Table 8 Bismuth-mediated three-component allylation reaction synthesis of iV-protected homoallylic amines...

Schaumann OO found that pretreatment of mice with 2-PAM 1 reduced inhibition of acetylcholinesterase in brain by paraoxon much more effectively than those by DFP and 217-A0. The finding of some protection against all three OP compounds could depend on direct reaction between the last two inhibitors and the oxime, with a reduction in inhibition of the enzyme. A similar consideration applies to the report by Bisa et al. that IV protected serum and brain cholinesterase from inhibition by paraoxon administered later at twice the LD5O. Although the same intraperitoneal dose of IV (7 mg) was found to protect the cholinesterase of rat serum and brain only incompletely from inhibition by DFP at 5 times the LD50, that of serum recovered its normal activity by 20 h after the dose of DFP, whereas that of brain required 26 h for recovery. 

Different syntheses of y-amino-/3-ketoeter derivatives from iV-protected L-aminoacids by Al,Al -carbonyldiimidazole activation and treatment with the magnesium enolate of hydrogen ethyl malonate are described. These compounds are useful intermediates in the preparation of active amino acid analogues, as illustrated and summarized in equation 103. 

Kobayashi K, Tominaga M, Asakawa Y, Aoyama Y (1993) Tetrahedron Lett 34 5121. For chiral recognition of iV-protect l amino acids by a metalloporphyrin, see Konishi K, Yahara K, Toshishige H, Aida T, Inoue S (1994) J Am Chem Soc 116 1337... 

Methylthiophene is metallated in the 5-position whereas 3-methoxy-, 3-methylthio-, 3-carboxy- and 3-bromo-thiophenes are metallated in the 2-position (80TL5051). Lithiation of tricarbonyl(rj6-iV-protected indole)chromium complexes occurs initially at C-2. If this position is trimethylsilylated, subsequent lithiation is at C-7 with minor amounts at C-4 (81CC1260). Tricarbonyl(i76-l-triisopropylsilylindole)chromium(0) is selectively lithiated at C-4 by tt-butyllithium-TMEDA. This offers an attractive intermediate for the preparation of 4-substituted indoles by reaction with electrophiles and deprotection by irradiation (82CC467). 

Recognizing the distinct difference in reactivity for each site of IV-protected 2,4,5-triiodoimidazole 23, Ohta s group successfully arylated 23 regioselectivcly [32, 33]. In the total synthesis of nortopsentin C, they coupled 23 with one equivalent of 3-indolylboronic acid 24 to elaborate imidazolylindole 25. The Suzuki reaction occurred regioselectively at C(2) of the imidazole ring. 

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