In chemistry, spiroketals are structural motifs composed of two heterocycles sharing one central carbon which makes them a subclass of spiro compound. Their structural specificity lays on the presence of one oxygen atom in each ring, in alpha of the spiro carbon. Although there are no rules about the size of each ring, the most widely encountered spiroketal are composed of five and six membered rings.
Occurrence in nature
Many natural products of biological interest contain 6,5- and 6,6-spiroketal moieties that can adopt various configurations. The first example of a spiroketals in the literature appeared before 1970, such as the triterpenoid saponins and sapogenins.
Then several works described the presence of spiroketals in various compounds. Like diarrheic shellfish poisoning (DSP) class of toxins containing in the
okadaic acid and ancanthafolicin. The most noticeable occurring spiroketals are the whole range of fruit fly pheromones.
Pharmacology interest
Due to its non-planar substructure, the spiroketal motif gain interest among the academical and industrial pharmaceutical research fields, both in
Drug design and development of screening libraries.
have been found in fungus and are antiparasitic drugs. The avermectins appear to paralyze and by potentiating the presynaptic release of gamma-aminobutyric acid, thereby blocking post-synaptic transmission of nerve impulses
Tofogliflozin is an inhibitor of human sodium glucose cotransporter 2 (hSGLT2) and was approved in 2014 in Japan for the treatment of Type 2 diabetes
Chemical synthesis
Acid catalyzed spiroketalisation
The most employed method to ring close spiroketal consists in the
hydrolysis of the dihydroxyketal in acidic conditions, but this method is not granting
Stereochemistry. Thus, several miscellaneous methods have emerged in order to control the stereoselectivity of the spirocyclisation.
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