Martinellic acid

An intramolecular azomethine ylide-mediated cyclization has been used to access the core 5 6 5 angular tricyclic structure of martinellic acid by Snider (Equation 113) <20010L4217>. Reaction of IV-benzylglycine 420 with the aldehyde 419 led to intramolecular cyclization, giving 421 in good yield. 

Witherup KM, Ransom RW, Graham AC, Bernard AM, Salvatore MJ, Lumma WC, Anderson PS, Pitzenberger SM, Varga SL (1995) Martinelline and martinellic acid, novel G-protein linked receptor antagonists from the tropical plant Martinella iquitosensis (Bignoniaceae). J Am Chem Soc 117 6682-6685... 

Hu et al. [104] disclosed that the spiro phosphine oxide ligand (/ )-30a is highly efficient for the Pd-catalyzed Heck reaction of cyclic and heterocyclic olefins with aryl triflates. An asymmetric domino Heck cyclization was established using catalyst Pd/(/ )-30a to form fused carbo- and heterocycles with excellent stereoselectivity (Scheme 42) [105]. This method was used in a short synthesis of (-)-martinellic acid, a primary ingredient in traditional eye medicine in South America. 

Martinellic acid binds to bradykinin receptors. This list appears to be incomplete, and certainly many more interactions with alkaloids will be discovered as soon as research is carried out which is directed towards these targets. 

Two pyrroloquinoline alkaloids, martinelline (49) and martinellic acid (50), have been isolated from an organic extract of root of Martinella iquitosensis A. Sampaio (Bigno-niaceae) by Witherup et al. (part of Merck s research group) as bradykinin receptor antagonists (Figure 10.11) [85]. The optical rotations of natural 49 and 50 were reported as [a]o +9.4 and -8.5, respectively, however the synthetic ( ) 50 showed a considerably larger value with the same sense ([a]o-122.7 [86,87] -164.3 [88]). A compound with the... 

Scheme 5.11 Sml -promoted cyclization protocol in the total synthesis of martinellic acid (40).

The heterocyclic core of martinelline and martinellic acid was prepared via the Povarov reaction between an aromatic imine derived from... 

A slightly more complex application of a Povarov reaction in total synthesis is the preparation of martinellic acid 504, reported by Batey in 2002 (Scheme 13.107) [197b]. Using the Povarov reaction, it was possible to bnild the highly snbstituted 1,2,3,4-tetrahydroquinoline core 503 in only two steps with good diastereoselectivity. 

SCHEME 13.107 Use of tiie Povarov reaction in total synthesis of martinellic acid 504. 

Reagent-free synthesis of 2,3,4-poly-substituted tetrahydroquinolines application to the formal synthesis of (+/-)-martinellic acid and martinelline. 

An enantioselective formal synthesis of martinelline using a similar method was developed by Yoshitomi et al. (Scheme 3.6) [24]. Isolated from the roots of Martinella iquitosensis, martinelline 44 and martinellic acid 43 are effective nonpeptidic bradykinin receptor agonists [25]. Furthermore, the structure of these alkaloids possesses an unusually fused pyrrolidinotetrahydroquinoline core, which attracted more attention. Yoshitomi et al. developed a similar, yet more powerful strategy to construct the quinoline core 41 from simple precursors of unsaturated aldehyde 39 with o-aminobenzaldehyde derivative 38. The product desired, 41, was obtained in quantitative yield and 99% ee. 

Ng PY, Masse CE, Shaw JT. Cycloaddition reactions of imines with 3-thiosuccinic anhydrides synthesis of the tricyclic core of martinellic acid. Org. Lett. 2006 8 3999-4002. 

Martinelline 136 and martinellic acid 137 are classified as pyrroloquinoline alkaloids. They were isolated from the roots of the tropical plant, Martinella iquitosensis, and show bradykinin receptor antagonistic activity. Hamada and co-workers reported on a synthesis of the chiral marti-nellin core structures 134 and 135 via organocatalytic cascade reaction. Anthranilaldehyde 130 and enal 131 underwent Michael-aldol reaction in the presence of (S)-... 

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