Protecting moieties ethyl

The sulfone moiety was reductively removed and the TBS ether was cleaved chemoselectively in the presence of a TPS ether to afford a primary alcohol (Scheme 13). The alcohol was transformed into the corresponding bromide that served as alkylating agent for the deprotonated ethyl 2-(di-ethylphosphono)propionate. Bromination and phosphonate alkylation were performed in a one-pot procedure [33]. The TPS protecting group was removed and the alcohol was then oxidized to afford the aldehyde 68 [42]. An intramolecular HWE reaction under Masamune-Roush conditions provided a macrocycle as a mixture of double bond isomers [43]. The ElZ isomers were separated after the reduction of the a, -unsaturated ester to the allylic alcohol 84. Deprotection of the tertiary alcohol and protection of the prima-... 

A concise synthesis of tetra-O-ethyl aldonolactam 83 starting from 1 has been reported [102]. After protection of its primary alcoholic moiety as a trityl ether, saponification and treatment with EtBr generated 80. Acidic hydrolysis liberated 81 that was esterified (tosylate). The latter was displaced with NaNs to give azide 82. Reduction of 82 resulted in lactam 83 (Scheme 24). 

The enolate species 2, derived from methacrylates with bulkier ester groups than MMA, are sterically protected against the access of BujAl under the above-mentioned conditions, even when the porphyrin moiety is a non-ortho-substituted tetraphenylporphyrin. An example is shown by the polymerization of ethyl methacrylate (EMA) using 1 (X=Me) as an initiator, where the growing species have an EtO group in the terminal enolate unit 2 (R=Et). After the addition of BujAl to the system, polymerization proceeded to 100% monomer conversion within 10 min. The Mn of the produced polymer was close to the expected value, and the MWD was narrow (Table 5, run 5). A similar result was obtained for the polymerization of isopropyl methacrylate (PMA) with the 1 (X= Mel- soBujAl system, which quantitatively gave a narrow MWD poly(methacr-ylate) with a predicted Mn (Table 5, run 6). 

The 1,3,4-oxadiazole moiety, in analogy to the 1,2,4-oxadiazole discussed in Section 11.2.5.1, has been used extensively as an ester or amide bioisostere, but also has only recently been applied as an amide replacement in actual peptide segments.1104-1071 The synthesis of the peptide surrogate 1,3,4-oxadiazole derivative 60 is shown in Scheme 18.11021 The N-protected amino acid Boc-Ala-OH (56) was coupled with ethanol to form the ester 57 which was subsequently reacted with hydrazine to form the amino acid hydrazide 58.11(1X1 The hydrazide 58 was reacted with ethyl oxalyl chloride at — 30 °C to room temperature to provide the diacylhydrazide 59. This intermediate was subsequently dehydrated with thionyl chloride in refluxing toluene to form the desired 1,3,4-oxadiazole 60 in >95% ee. Although the overall yields are only moderate, the reported enantioselectivities of the final compounds are very good (Table 4).11021... 

A new alcohol and phenol protective group, the l-[(2-trimethylsilyl)ethoxy]ethyl moiety, readily introduced using 2-(trimethylsilyl)ethyl vinyl ether and catalytic pyridinium p-toluenesulfonate (PPTS), has been described76. Cleavage is achieved under near-neutral conditions using TBAF monohydrate (equation 16). 

Melphalan and the racemic analog have been prepared by two general routes (Scheme I). In Approach (A) the amino acid function is protected, and the nitrogen mustard moiety is prepared by conventional methods from aromatic nitro-derivatives. Thus, the ethyl ester of N-phthaloyl-phenylalanine was nitrated and reduced catalytically to amine I. Compound I was reacted with ethylene oxide to form the corresponding bis(2-hydroxyethyl)amino derivative II, which was then treated with phosphorus oxychloride or thionyl chloride. The blocking groups were removed by acidic hydrolysis. Melphalan was precipitated by addition of sodium acetate and was recrystallized from methanol. No racemization was detected [10,28—30]. The hydrochloride was obtained in pure form from the final hydrolysis mixture by partial neutralization to pH 0.5 [31]. Variants of this approach, used for the preparation of the racemic compound, followed the same route via the a-acylamino-a-p-aminobenzyl malonic ester III [10,28—30,32,33] or the hydantoin IV [12]. 

The three orthogonally removable lysine protecting groups we use here are Fmoc (9-fluorenyl methoxy carbonyl), cleavable with 20% base, preferably with 20% piperidine or 3% DBU (l,8-diazabicyclo[5.4.0]undec-7-ene) (18), Dde (1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-ethyl), cleavable with 2% hydrazine, and Aloe (allyloxy carbonyl), cleavable with palladium. Hydrazine also removes Fmoc, and thus it can be applied only if no Fmoc groups are present on the growing peptide chain. Acid-sensitive amino protecting groups available are Boc (tert-butyloxy carbonyl), cleavable with 90% TFA, and Mtt (4-methyl-trityl), cleavable with 1% TFA. We use Boc for the protection of the N-terminal moieties of N-terminal amino acids in each peptide chain as well as at the N-terminus of the scaffold. 

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