Amino acids TBDMS deriv

A. Mass Spectra of TBDMS Derivatives of Amino Acids... 

Loss of (C4H9 + CO) from TBDMS derivatives of amino acids Caffeine [-C(0)N(CH3)C(0)-]... 

Retention times and suggested ions for selected ion monitoring (SIM) of TBDMS derivatives of AAs are given in Table 9.1 and the GC separation is shown in Figure 9.1. Amino acids should be derivatized prior to separation. The TBDMS derivatives are preferred and stable for at least 1 week. 

The loss of -C(0)OSi(CH3)2C(CH3)3 is characteristic of TBDMS derivatives of amino acids... 

Postsynthetic intramolecular alkylation of a cysteine thiol group with a bromo amino acid has also been proposed/431 but this approach is limited by the low coupling efficiency of the bromo amino acid in the peptide synthesis due to a competing intramolecular cyclization reaction. A promising new approach consists of using suitably protected cysteine and homoserine derivatives for the peptide synthesis, whereby the side-chain hydroxy group of homoserine is protected as the TBDMS derivative which is converted on resin into the chloro derivative with freshly prepared triphenylphosphine dichloride. Upon cleavage from the resin, cyclization is performed in solution as shown in Scheme 11144]... 

Yamaguchi et al. also showed that Rb-L-prolinate catalyzes enantioselective addition of nitroalkanes to several acyclic and cyclic enones [25, 26]. For acyclic enone acceptors the best result, i.e. 74% yield and 68% ee of the S product, was achieved in the addition of 2-nitropropane to -3-penten-2-one (40a, Scheme 4.13) [25]. Screening of several proline derivatives and cyclic amino acids of other ring size resulted in the identification of the O-TBDMS-derivative of 4-hydroxyproline as the best catalyst for addition of nitrocyclohexane to cycloheptenone. In this particular reaction 74% yield and 86% ee were achieved [26]. 

As has been demonstrated, 2-(trimethylsilyl)ethoxymethyl (SEM) esters are selectively removed from amino acids and peptide derivatives in the presence of the most common N- and O-protecting groups applied in peptide chemistry including the urethane-type Boc, Z, Fmoc, and Troc as well as Bzl, tBu, and TBDMS ethers.The SEM ester is removed by acidolysis or with a fluoride ion source, e.g. TBAF in THF or HMPA or with aqueous HF in MeCN (—10°C).f l Deprotection with magnesium bromide in EtjO represents an even milder alternative that allows increased selectivity toward fluoride-labile silyl ethers or Fmoc groups. The SEM esters are prepared in 60-80% yield by stirring a mixture of 0.25 M N-protected amino acids in DMF with 0.8 equivalents of SEM-Cl and 1.1 equivalents of lithium carbonate at room temperature for 16 hours. 

Silyl ethers of hydroxy amino acids have been employed in both solid-phase and solution peptide synthesis. Since the TBDMS and TBDPS ether groups are stable to piperidine and other basic reagents, these derivatives of Ser and Thr (Tables 8 and 9) can be used in the Fmoc strategy.Homodetic peptides and depsipeptides have also been synthesized using TBDMS hydroxy protection for phenyllactic acid and hydroxyisovaleric acid, respectively. 

Many methods have been used to synthesize u and benzyl derivatives of Thr and Ser. These include reaction of benzyl bromide with Ser under basic conditions, acid-catalyzed addition of benzyl alcohol to Thr, and acid-catalyzed addition of isobutylene for tBu protection [57-61]. Benzyl and rBu protection can also be achieved via formation of 2,2-difluoro-1,3,2-oxazaborolidin-5-ones by reaction of the sodium salt of Thr or the lithium salt of Ser with BF3. Treatment with isobutylene or benzyl 2,2,2-trichlo-roacetimidate followed by destruction of the 2,2-difluoro-1,3,2-oxazaboro-lidin-5-ones generates the desired side-chain protected amino acid [62] (Scheme 14). The Trt and TBDMS groups are obtained via their respective chlorides in the presence of base [54,56] (Scheme 15). 

TBDMS derivatives of amino acids. Although quantitative derivatization was achieved with MTBSTFA containing 1% of TBDMCS in DMF by heating at 75 °C for 30 min, two peaks were obtained for arginine. The size of the TBDMS group prevents multiple silylation of the nitrogen atoms. The El mass spectra are sufficiently characteristic to make the TBDMS derivatives very useful for GC-MS analysis, with detection limits at the picomole level [362,364). Methane Cl mass sp>ectra have also been found to be of use in confirming the nature of TBDMS derivatives [3651. 

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