SASRIN

Table 9.1 shows the method s versatility across several solid-support types. Care must be taken to dry the tentagel resins by lyophilization for 24 h before subjecting them to the reaction conditions. In the examples shown, quantitative conversions were obtained as determined by elemental analysis and 13C NMR. The mild reaction conditions are most evident by the quantitative conversion of SASRIN resin to its corresponding chloromethyl... 

Preparation of AMEBA Resin A from SASRIN Resin,... 

A total of 10.0 g (8.9 mmol) SASRIN resin2 (note 1) was washed with N,N-dimethyIfonnamide (DMF 2 x 25 mL), methanol (MeOH 2 x 25 mL), and dichloromethane (DCM note 2 2 x 25 mL), and dried under vacuum (0.5 torr) at 70°C overnight. To a suspension of the dried SASRIN resin in lOOmL of methyl sulfoxide (DMSO note 2) and 25 mL of DCM was added 12.4 mL (89 mmol, 10.0 Eq.) triethylamine (note 2) followed by 7.1 g (44.5 mmol, 5.0 Eq.) sulfur trioxide-pyridine complex (note 2). The suspension was shaken on a radial arm at room temperature overnight (note 3) filtered on a glass frit and washed with DCM (3 x 100mL), DMSO (3 x lOOmL), DCM (3 x lOOmL), and tetrahydrofuran (THF 3 x 100 mL) and dried under vacuum (0.5 torr) at room temperature to give 10.0 g Ameba resin (notes 4 and 5). 

SASRIN resin (0.89 mmol/g) was obtained from Bachem Bioscience, Inc., Product D-1295, Lot 507127. Checkers... 

Ameba resin A loading was assumed to be 0.89 mmol/g, based on the loading of the starting SASRIN resin. 

Liming and coworkers (56) also used the Fmoc group for temporary amino protection and employed a commercial resin (SASRIN , trademark of Bachem, Switzerland) having a dialkoxybenzyl anchoring group. The synthesized glycopeptide could be cleaved from the resin with 1% trifluoroacetic acid in dichloromethane. 

The reaction of A-hydroxyphthalimide 178 with Wang or Sasrin 179 resins under Mit-sunobu conditions to give 180 is one of the common preparative routes to O-immobilized hydroxylamine 181 (Scheme 80). ... 

Solid-phase synthesis of pyrido[2,3 pytirtiidines 514 was achieved by Hantzsch condensation of Wang resin-supported Knoevenagel derivative 513 with 6-aminouracil derivatives 512 as an a-oxo enamine component in the presence of ceric ammonium nitrate (CAN) in DMA followed by hydrolysis with TFA in CH2GI2. Compound 513 was prepared by treatment of a hydroxylated polymer, such as Wang or Sasrin resin, with diketene, followed by condensation with benzaldehyde (Equation 41) <1996TL4643>. 

Sasrin-derived sulfonates have been prepared in the presence of DMAP, without significant loss of sulfonate through displacement by DMAP [201]. 

As illustrated by the examples in Table 3.9, resin-bound 4-alkoxybenzylamides often require higher concentrations of TFA and longer reaction times than carboxylic acids esterified to Wang resin. For this reason, the more acid-sensitive di- or (trialkoxy-benzyl)amines [208] are generally preferred as backbone amide linkers. The required resin-bound, secondary benzylamines can readily be prepared by reductive amination of resin-bound benzaldehydes (Section 10.1.4 and Figure 3.17 [209]) or by A-alkyla-tion of primary amines with resin-bound benzyl halides or sulfonates (Section 10.1.1.1). Sufficiently acidic amides can also be A-alkylated by resin-bound benzyl alcohols under Mitsunobu conditions (see, e.g., [210] attachment to Sasrin of Fmoc cycloserine, an O-alkyl hydroxamic acid). 

Thiomorpholinones have been prepared on cross-linked polystyrene by intramolecular thioether formation and by the lactamization of suitable amino acids (Entries 8 and 9, Table 15.34). l,3,5-Thiadiazine-2-thiones (Entry 11, Table 15.34) are not stable towards TFA/DCM (1 1) and have therefore been prepared on Sasrin cleavage from the support could be achieved using 3% TFA in DCM [411],... 

Because no treatment with acid is required during peptide assembly, peptide synthesis with Fmoc amino acids can be conducted on acid-sensitive supports (e.g. Tenta-gel) and with acid-labile linkers. Wang resin is suitable for most purposes, but other supports, such as Sasrin or 2-chlorotrityl resin, can also be used. CPG, macroporous... 

The linear decapeptide was synthesized on Fmoc-Lys(Boc)-SASRIN-resin (2.0 g, substitution 0.6 mmol-g1) applying standard Fmoc strategy based on DIC/HOBt activation with DIPEA as base. After removal of the last Fmoc group, the peptide was cleaved from the resin and cyclized as described in Section 13.1.1.1.1 yield 0.671 g (68%) ESI-MS 1646.3 [M + H]+, 823.8 [M/2+H]+. 

Solid-Phase Assembly of Fmoc-Ahx-Lys(Ahx-Fmoc)-Lys(Ahx-Fmoc)-Tyr(tBu)-Gly-SASRIN-Resm (17, A=Fmoc C = tBu) [84l... 

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