Hispanopedia WikiLa introducción intramolecular de agliconas es una estrategia sintética para la construcción de glicanos . Este método se utiliza generalmente para la formación de enlaces glucosídicos difíciles .
Introducción
Las reacciones de glicosilación son muy importantes en la química de los carbohidratos , ya que conducen a la síntesis de oligosacáridos , preferiblemente de forma estereoselectiva. Se ha demostrado que la estereoselectividad de estas reacciones se ve afectada tanto por la naturaleza como por la configuración del grupo protector en C-2 del anillo donador de glicosilo . Mientras que los 1,2- trans- glicósidos (p. ej., α-manósidos y β-glucósidos) se pueden sintetizar fácilmente en presencia de un grupo participante (como OAc o NHAc) en la posición C-2 del anillo donador de glicosilo, los 1,2- cis -glicósidos son más difíciles de preparar. Los 1,2- cis -glicósidos con configuración α (p. ej., glucósidos o galactósidos) a menudo se pueden preparar utilizando un grupo protector no participante (como Bn o All) en el grupo hidroxilo C-2 . Sin embargo, los 1,2- cis- glucósidos con configuración β son los más difíciles de obtener y representan el mayor desafío en las reacciones de glicosilación.
Uno de los enfoques más recientes para preparar 1,2 -cis -β-glucósidos de manera estereoselectiva se denomina " Entrega intramolecular de aglicona ", y se han desarrollado varios métodos basados en este enfoque. [ 1 ] En este enfoque, el aceptor de glicosilo se une al grupo protector C-2-O (X) en el primer paso. Tras la activación del grupo donador de glicosilo (Y) (generalmente SR, OAc o Br) en el siguiente paso, la aglicona unida atrapa el ion oxocarbenio en desarrollo en C-1 y se transfiere desde la misma cara que OH-2, formando el enlace glucosídico de manera estereoselectiva. El rendimiento de esta reacción disminuye a medida que aumenta el volumen del alcohol.
Métodos de administración intramolecular de agliconas (IAD)
Sujeción de carbono
Unión catalizada por ácido a éteres de enol
In this method, the glycosyl donor is protected at the C-2 position by an OAc group. The C-2-OAc protecting group is transformed into an enol ether by the Tebbe reagent (Cp2Ti=CH2), and then the glycosyl acceptor is tethered to the enol ether under acid-catalysed conditions to generate a mixed acetal. In a subsequent step, the β-mannoside is formed upon activation of the anomeric leaving group (Y), followed by work up.[2]
Iodonium tethering to enol ethers
This method is similar to the previous method in that the glycosyl donor is protected at C-2 by an OAc group, which is converted into an enol ether by the Tebbe reagent. However, in this approach, N-iodosuccinimide (NIS) is used to tether the glycosyl acceptor to the enol ether, and in a second step, activation of the anomeric leaving group leads to intramolecular delivery of the aglycon to C-1 and formation of the 1,2-cis-glycoside product.[3]
Iodonium tethering to prop-1-enyl ethers
The glycosyl donor is protected at C-2 by OAll group. The allyl group is then isomerized to a prop-1-enyl ether using a rhodium hydride generated from Wilkinson's catalyst ((PPh3)3RhCl) and butyllithium (BuLi). The resulting enol ether is then treated with NIS and the glycosyl acceptor to generate a mixed acetal. The 1,2-cis (e.g. β-mannosyl) product is formed in a final step through activation of the anomeric leaving group, delivery of the aglycon from the mixed acetal and finally hydrolytic work-up to remove the remains of the propenyl ether from O-2.[4]
Oxidative tethering to para-methoxybenzyl (PMB) ethers
In this method, the glycosyl donor is protected at C-2 by a para-methoxybenzyl (PMB) group. The glycosyl acceptor is then tethered at the benzylic position of the PMB protecting group in the presence of 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The anomeric leaving group (Y) is then activated, and the developing oxocarbenium ion is captured by the tethered aglycon alcohol (OR) to give 1,2-cis β-glycoside product.[5]
Solid-supported oxidative tethering to para-alkoxybenzyl ethers
This is a modification of the method of oxidative tethering to a para-methoxybenzyl ether. The difference here is that the para-alkoxybenzyl group is attached to a solid support; the β-mannoside product is released into the solution phase in the last step, while the by-products remain attached to the solid phase. This makes the purification of the β-glycoside easier; it is formed as the almost exclusive product.[6]
Silicon tethering
The initial step in this method involves the formation of a silyl ether at the C-2 hydroxy group of the glycosyl donor upon addition of dimethyldichlorosilane in the presence of a strong base such as butyllithium (BuLi); then the glycosyl acceptor is added to form a mixed silaketal. Activation of the anomeric leaving group in the presence of a hindered base then leads to the β-glycoside.[7]
A modified silicon-tethering method involves mixing of the glycosyl donor with the glycosyl acceptor and dimethyldichlorosilane in the presence of imidazole to give the mixed silaketal in one pot. Activation of the tethered intermediate then leads to the β-glycoside product.[8]
See also
References
- ↑Cumpstey, I. Carbohydr. Res.2008, 343, 1553–1573
- ↑Barresi, F.; Hindsgaul, O. J. Am. Chem. Soc.1991, 113, 9376–9377
- ↑Ennis, S. C.; Fairbanks, A. J.; Slinn, C. A.; Tennant-Eyles, R. J.; Yeates, H. S. Tetrahedron2001, 57, 4221–4230
- ↑Seward, C. M. P.; Cumpstey, I.; Aloui, M.; Ennis, S. C.; Redgrave, A. J.; Fairbanks, A. J. Chem. Commun.2000, 1409–1410
- ↑Ito, Y.; Ogawa, T. Angew. Chem. Int. Ed. Engl.1994, 33, 1765–1767
- ↑Ito, Y.; Ogawa, T. J. Am. Chem. Soc.1997, 119, 5562–5566
- ↑Stork, G.; Kim, G. J. Am. Chem. Soc.1992, 114, 1087-1088
- ↑Stork, G.; La Clair, J. J. J. Am. Chem. Soc.1996, 118, 247–248
- Carbohydrate chemistry