Acyl migration, novel

The Merck compound MK-0608 is a 2 -C-Me-7-deaza-adenosine analog, which has recently been reported to show a 5.7 log drop in viral load in HCV-infected chimpanzees after dosing QD at 2mg/kg (Olsen 2006). An efQcient and practical process for preparing kilogram quantities has been described (Bio et al. 2004). The 12-step synthesis provides an impressive 35% overall yield and starts from the inexpensive diacetone-D-glucose. The synthesis features a novel acyl migration in route to prepare the key crystalline furanose diol intermediate (Fig. 5). The conditions... 

Y Sohma, M Sasaki, Y Hayashi, T Kimura, Y Kiso. Novel and efficient synthesis of difficult sequence-containing peptides through O-N intramolecular acyl migration reaction of O-acyl isopeptides. Chem Commun 124, 2004. 

Crossover experiments have been used to establish that the novel N to C acyl migration reaction of acyclic imides (69), to give o -amino ketones (70), proceeds by intramolecular reaction of the base-generated carbanion. ... 

The formation of tluorinated Q -hydroxy-jS-imino esters (180) by treatment of fluorinated imino ethers (179) with lithium 2,2,6,6-tetramethylpiperidide has been reported. A possible explanation for this interesting intramolecular rearrangement is proposed in Scheme 64. Acyclic imides derived from primary benzylic amines and amino acid esters have been found to undergo a novel nitrogen to carbon acyl migration via a base-generated carbanion to yield the corresponding a-amino... 

Hara, O. Ito, M. Hamada, Y. Novel N-C acyl migration reaction of acyclic imides a facile method for a-amino ketones and / -amino alcohols. Tetrahedron Lett. 1998, 39, 5537—... 

Photolysis of [(Z)-2-(acyloxy)ethenyl]carbene complexes (= 4-acyloxy-1-chroma-l,3-dienes) (CO)sCr=C(OEt)-CH=C(OCOR1)R (Z)-169 (R = C6H5, t-Bu, c-Pr R1 = C6H5, c-Pr, c-C7H7CH2, f-Bu, Me2C=CH) with UV light of >300 nm affords 2-butene 1,4-diones R CO —C(OEt)=CH — COR (E)-170 (60-68%) by a novel metal-mediated acyl migration. Compounds (Z)-171 and furans 172 are formed as minor products (Scheme 72).4g... 

Sohma Y, Sasaki M, Hayashi Y, Kimura T, Kiso Y. Design and synthesis of a novel water-soluble A(il-42 isopeptide an efficient strategy for the preparation of Alzheimer s disease-related peptide, Api-42, via O-N intramolecular acyl migration reaction. Tetrahedron Lett. 2004 45 5965-5968. 

Problem 1. An Obvious and Yet Novel 1,4-Acyl Migration Problem 2. A Classical [2 -I- 4] Diels-Alder Cycloaddition Followed by Rearrangement... 

Owens, T. D., Araldi, G. L., Nutt, R. F., Semple, J. E. Concise total synthesis of the prolyl endopeptidase inhibitor eurystatin A via a novel Passerini reaction-deprotection-acyl migration strategy. Tetrahedron Lett. 2001,42, 6271-6274. 

A novel approach was developed very recently by Kita et al. [15]. DKR of allylic alcohols was performed by combining a lipase-catalyzed acylation with a racemization through the formation of allyl vanadate intermediates. Excellent yields and enantioselectivities were obtained. An example is shown in Figure 4.4. A limitation with this approach for the substrates shown in Figure 4.4 is that the allylic alcohol must be equally disubstituted in the allylic position (R = R ) since C—C single bond rotation is required in the tertiary alkoxy intermediate. Alternatively, R or R can be H if the two allylic alcohols formed by migration of the hydroxyl group are enantiomers (e.g. cyclic allylic acetates). 

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