ChemInform Abstract: Observations Made in Exploring a Pyridinium Salt Photochemical Approach to the Synthesis of (+)‐Lactacystin.

Abstract

Amino acids U 0400Observations Made in Exploring a Pyridinium Salt Photochemical Approach to the Synthesis of (+)-Lactacystin. -The key step in the synthesis of (+)-lactacystin (V), a biologically interesting proteasome inhibitor, involves photocyclization of a cyclopenta-fused pyridinium salt using the newly synthesized compound (I) as model substrate. Especially the stereoselective formation of the tricyclic carbamate (IV) is described as potentially compatible with the general strategy. -(ZHOU, J.; GONG, M.; MARIANO*, P. S.; YOON, U. C.; Bull. Korean Chem. Soc. 29 (2008) 1, 89-93; Dep. Chem. Chem. Biol., Univ. N. Mex., Albuquerque, NM 87131, USA; Eng.) -H. Haber 23-188

Photochemical rearrangements in organic synthesis and the concept of the photon as a traceless reagent

“…129 Some examples are shown in Figure 5: mannostatin A 130 , trehazolin 131 , cephalotaxine 132 or lactacystin. 133 Often complex carbon skeletons such as spirocyclic compounds are generated in the photochemical key step of these syntheses. Photochemical electrocyclization of pyridine derivatives was also applied to interconversions of compounds belonging to a natural product family.…”

Photochemical Rearrangements in Heterocyclic Chemistry

“…Using continuous flow technology, the photochemical reaction was carried out on multi gram scale with a productivity of 3.7 g L -1 h -1 . [88] The photochemical pathway gives an attractive approach, leading to versatile intermediate compounds which can be used for the total synthesis of molecules such as mannostantin A, trehazolin derivatives, [89] cephalotaxine [90] or even Lactacystin [91] (Figure 2). Mechanistic and theoretical studies performed by Damiano et al explain in details how the irradiation of pyridinium salts provides the stereocontrolled synthesis of a huge range of molecular structures such as bicyclic aziridines, fused heterocycles and functionalised aminocyclopentenes.…”

On the photochemical reaction of pyridinium salts with nucleophiles

“…The synthesis of aminocyclopentene derivatives through photochemical isomerization of pyridinium salts, coupled with a desymmetrization performed with acetylcholinesterase from Electrophorus electricus opened the possibility of the use of this reaction in organic synthesis [8]. This way, this type of compounds has been used in the synthesis of ( +)-mannostatin A [9,10], (−)-allosamizoline aminocyclopentitol [11], 3-amino-3-deoxyaldopentoses [12], polyhydroxylated indolizidines [13,14], ( +)-castanospermine [14], trehazolin aminocyclitol [15], and ( +)-lactacystin [16] (Fig. 1) [17].…”