Iridoids functions

Stephens PJ, Pan JJ, Krohn K. Determination of the Absolute Configurations of Pharmacological Natural Products via Density Functional Theory Calculations of Vibrational Circular Dichroism The New Cytotoxic Iridoid Piismatomerin. Journal of Organic Chemistry 2007 72(20) 7641-7649. 

It is also extremely common amongst natural iridoids and secoiridoids, to have a double bond between C-3 and C-4, and a carboxylation at C-11. Changes in functionalities at various other carbons in iridoid and secoiridoid skeletons are also found in nature, as shown below. 

Iridoid and secoiridoid glycosides with modified functionalities... 

Diverse in structure, these include iridoids and terpenes thought to promote normal bowel function. 

Whitesell and Minton have synthesized (- )-xylomollin (408), the only trans-fiised iridoid, from the racemic bicyclic diene 409. Control of the stereochemistry was effected in the first step by addition of the glyoxylate 410. The two products were separated and the major one, 411, was reduced with lithium aluminum hydride. Conversion of the primary alcohol to a methyl group, with concomitant inversion of stereochemistry at the secondary alcohol carbon atom was carried out by protection of the primary alcohol function (fert-butyldimethylsilyl), tosylation of the secondary hydroxyl, then removal of the silyl group with formation of an epoxide with inversion, and reduction (LiEtaBH) of the epoxide. The remaining steps are shown in Scheme 36. It remains to point out that isoxylomoUin (412) was produced preferentially, and is indeed formed from xylomollin (408) slowly in methanolic solution. ... 

The great advantage of the type of approach used by Vandewalle is that a variety of stereochemistries of different substituents around a bicyclo[2.2. l]hep-tane skeleton is accessible using different Diels-Alder reactions, making a stereospecific approach to many iridoids possible by relatively simple manipulations of the functional groups. 

Occasionally, plant alkaloids of terpenoid origin are sequestered by insects. For example, larvae of many species of sawfly are chemically protected by toxic metabolites they sequester from their host plants. This includes iridoid glycosides (see Section 2.04.3) and a group of steroidal alkaloids produced by plants of the genus Veratrum, such as zygadenine (149). In some cases, sawfly larvae have been shown to further metabolize sequestered Veratrum alkaloids for example, zygadenine is derived from hydrolysis of the ester functionalities in sequestered protoveratrine A (150). ... 

Numerous iridoids are involved in plant-animal interactions e.g. the defensive function of this type of compounds in ants. From the pharmacological standpoint, the applications of this class of compounds are rather limited. Some iridoids have anti-inflammatory activity, which is weak by the oral route and stronger by topical application e.g. 1 mg of aucubin, verbenalin, or loganin have an activity almost similar to that of 0.5 mg of indomethacin on the TPA-induced mouse ear edema. Some are ingredients in various forms of allopathic medications (valerian), others are typically, phytotherapeutic products (devil s claw, olive tree). Others receive attention for their non-pharmaceutical applications (yellow gentian). The hepatoprotective effects of picrosides I and II from kutkin, the crude active fraction in Picrorhiza kurroa is well known and documented. 

The hemiacetalic C-2 fimction can be blocked by a sugar residue, affording the methylcyclopentanoid monoterpenes known as glycosidic iridoids. Otherwise the same function can be esterified giving rise to the non-glycosidic iridoids of plumeria or valeriana-type ( fig.6 ). 

Reduction of one or both aldehydic functions of iridodial or iridotrial, responsible for the closure of the pyranoid ring, gives rise to the non-glycosidic iridoids, known as iridodiols, generally having only the methylcyclopentanoid moiety ( fig.8 ). 

The hemiacetalic iridoidic intermediate 49 obtained has been successively transformed into the two corresponding enantiomers methylacetals 50 and 50a and the secondary alcoholic function on the cyclopentane ring oxidised to a carbonyl group (enantiomeric mixture 51 and 51a obtained). 

The iridoid natural products contain a functionally and stereochemically rich scaffold, which has inspired chemists to design a diverse range of strategies for their construction. Biichi and coworkers reported the first total synthesis of the iridoid aglycone ( )-genipin (25) in 1967 (Scheme 5). Pivotal to... 

Based on our experiences with the NHC-catalyzed synthesis of dihydropyra-nones, we thought it conceivable that ot,p-unsaturated enol ester 51a could be converted to the iridoid cyclopenta[c]pyran core (i.e., 52a) (Scheme 11). In turn, it was envisaged that the required unsaturated enol ester 51a could be prepared via acylation of methyl formyl acetate (53a) with enantioenriched acyl chloride 54. The NHC-catalyzed rearrangement would only prove viable if it proceeded with chemoselectivity, due to the presence of additional ester functionality in enol ester 51a, and stereoselectively, to provide the correct diastereomer of 52a for the natural product. Although it was unclear whether these selectivities could be achieved, or whether the reaction would proceed with substrates annulated about the a,p-unsaturation, it was envisaged that this study would, at the very least, allow the limitations of the NHC catalysis to be examined. From the iridoid core 52a, completion of the total synthesis would require the chemo- and stereoselective reduction of the lactone to the lactol, followed by glycosylation. 

Asperuioside. A. and the compounds listed in the table are iridoid glucosides with an intramolecular lactone ring or an acid function. Some of the acids may be formed during work-up. 

BoschnaiosMle. B. belongs to the iridoid glucosides with a C,o aglycone possessing an aldehyde function. C15H24O8, Mr 344.36, amorphous, [a]o -104°... 

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