N-Fmoc

Specifically, the carboxylates of N -Fmoc-protected (and side chain-protected) N-substituted glycines were activated and then coupled to the secondary amino... 

N -Fmoc serine benzyl ester 2, which could be prepared as shown or purchased commercially, was smoothly converted to the crystalHne O-methylthiomethyl (MTM) ether 3 in high yield via a Pummerer-Hke reaction using benzoyl peroxide and dimethyl sulfide in acetonitrile [39]. This common intermediate was used to synthesize both 5 and 8 [40]. Both Ogilvie [41] and Tsantrizos [42] had reported that I2 was an effective activator with similar MTM ether substrates. The H promoted nucleosidation reaction between O-MTM ether 3 and bis-silylated thymine 4 produced the nucleoamino acid 5 in 60% isolated yield (100% based on recovered 3). Hydrogenolytic deprotection of the benzyl ester with H2, Pd/C in MeOH gave the thymine-containing nucleoamino acid 6 in quantitative yield. 

Takahashi and coworkers described an effective sialylation method utilizing the N-Fmoc, N-Troc and N-trichloroacetyl-P-thiophenyl sialosides (Scheme 4.6d) [167]. It was found that the N-Troc derivative of N-acetylneuraminic acid performed better than the corresponding N-Fmoc derivative. An N-Troc P-thiosialoside was applied for the synthesis of glycosyl amino acids by one-pot glycosylation [167]. Importantly, it was found that the N-Troc protecting group could be converted into an acetamido moiety without causing racemization of the peptide. 

N-Fmoc-aminooxy-2-chlorotrityl polystyrene (212 mg, 0.95 mmol g 1,0.2 mmol) was placed in a reaction column (1.0 cm diameter alternatively, an appropriate reaction vessel can be used, e.g., Quest 210 synthesizer 5-mL reaction vessel) and preswollen in DCM DMF (1 1, 3mL) for 24 h (note 4). The resin was then washed with DMF (10min, 2.5 mL min-1) and Fmoc-depro-tected by treatment with 20% v/v piperidine in DMF (10 min, 2.5mL min-1). The resin was then washed with DMF (lOmin, 2.5 mL min ), after which excess DMF was removed. 

N-FMOC-AMINOOXY-2-CHLOROTRITYL POLYSTYRENE RESIN FOR HIGH THROUGHPUT SYNTHESIS OF HYDROXAMIC ACIDS 85... 

HN Gopi, VV Suresh Babu. Zinc-promoted simple synthesis of oligomer-free N -Fmoc-amino acids using Fmoc-Cl as an acylating agent under neutral conditions. J Pept Res 55, 295, 2000. 

Synthesis via symmetrical anhydrides of N-Fmoc amino acids... 

Other related reactions involve TV-fluorenylmethyloxycarbonyl (N-Fmoc) AAs and aliphatic aldehydes (83JOC77) or substituted /-butoxycarbonyl (N-Boc) Aas and 2,2-dimethyoxypropane (acetone dimethyl ketal) (84TL5855 87JOC2361 88TL2019), as well as A-(dimethylthio)methylene derivatives of an AA and aromatic aldehydes [89JCS(P1)1577]. 

In addition to incorporating the 4-(2-aminoethyl)dibenzofuran-6-propanoic acid template into small peptides where a reverse turn is desired, we have also recently incorporated this template into a mini-protein called the PIN WW domain. WW domains have a three-stranded antiparallel p-sheet structure that mediates intracellular protein-protein interactions. 31 Substitution of this 3-turn mimetic into loop 1 of the PIN WW domain leads to a folded, three-stranded, antiparallel p-sheet structure with a stability indistinguishable from that of the all a-amino acid sequence. The template-incorporated PIN WW domain (11) was synthesized by an Fmoc-based solid-phase peptide synthesis strategy (Scheme 8), utilizing N-Fmoc-protected 4-(2-aminoethyl)dibenzofuran-6-propanoic acid 10. 11 The synthesis of 10, similar to that of 8, has been published.1 1 ... 

Chen and co-workers at Procter and Gamble developed a traceless synthesis of 2,5-diketopiperazines [18b] by employing the universal Rink-isocyanide resin. The Ugi-4CR between the resin, aldehydes, amines, and N-Fmoc-protected a-amino acids afforded the resin-bound dipeptide derivatives 131 which were N-deprotected on treatment with piperidine in DMF. Cyclization by heating with 10% AcOH in DCE smoothly provided the desired diketopiperazines 132 in good yields (Scheme 2.47). 

Golebiowski et al. reported the solid-phase [92] and the solution-phase [93] syntheses of bycyclic diketopiperazines which were of great interest because their conformation was similar to the type-1 /i-turn motif. A Merrifield hydroxymethyl resin was esterified with a-N-Boc-fi-N-Fmoc-L-diaminopropionic acid and then mono-deprotected at the />-N with piperidine. Ugi-4CR of the resulting resin-bound amine gave the resin-bound adducts 168. Subsequent N-Boc deprotection and intramolecular N-alkylation afforded the ketopiperazines 169. The diketopiperazines 170 were formed via N-Boc amino acid coupling followed by N-Boc deprotection... 

The preparation of immobilized catalysts related to the imidazolidinone-type organocatalyst 13 and their application in the asymmetric Diels-Alder reaction was reported by Pihko and co-workers [9]. The reactivity of the immobilized catalysts depended on the type of solid support. The silica-supported imidazolidinone 24, which was prepared starting from N-Fmoc-protected L-phenylalanine, was found to be a highly active organocatalyst. Several dienes and a,/i-un saturated aldehydes have been successfully used in the presence of only 3.3 to 20 mol% 24, usually... 

For the synthesis of epopromycin B, precursor 47 was prepared via the addition of (S)-N-Fmoc-leucinal, 46, to HFIPA, 43, at -55 °C (Scheme 5.10) [67]. The reaction afforded, after methanolysis, two diastereoisomers the syn product 49 was obtained in 70% yield and in 99% ee, and the anti isomer 50 was obtained in 2% yield and in 99% ee. It should be noted that the hexafluoroisopropyl group was converted to the corresponding methyl ester in the alcoholysis step. The major syn isomer 49 was transformed to the epoxy end-product 51. 

In solution, phase amino acid derived methyl ester N-Fmoc-Tyr-OMe 4 was successfully condensed under Mitsunobu conditions with 2,3,4,6-tetra-Oacetyl-D-glucose 2 to afford the fully protected glucosylamine 5. The reaction provides products of analytical purity and predictable stero-chemistry, as confirmed by H/ C NMR. Synthetic conditions and protective groups for glycopeptides synthesis have been investigated. Mitsunobu conditions employed in solution phase are based on the improved redox system l,l -azodicarbonyldipiperidine (ADDP)—tributylphosphine (TBP) in... 

Fig. 17.7 Solid phase synthesis to obtain aminoindoline alkaloid-like tricyclic compounds by in situ aza Michael approach - (a) alkylsilyl linker-based polystyrene macrobeads (1.0 equiv),TfOH (6.0 equiv), 2,6-lutidine (10.0 equiv), 14 (0.5 equiv) (b) (i) 20% piperidine (ii) N-Fmoc amino acid chloride, collidine (iii) 20% piperidine.

---