Nine-membered macrocyclic

A 2 2 cyclocondensation process was a by-product when the crab-like cyclization was used to form the nine-membered macrocycles. Thus, [18]N(, accompanied the desired [9]N3 when the crab-like starting material was reacted with a primary amine. An exception to this general process was observed for the cyclization reaction using the monoamine derivative of diethylene glycol where only the [9]N3 formed (Krakowiak et al., 1990b). Presumably,... 

It is interesting to note that the nine-membered macrocycle must be the result of homocouphng of the corresponding nine-membered bisboronate. With these macrocycles in hand, Jasti developed a reductive aromatization technique that circumvented the 1,2-phenyl shift observed under acidic or Lewis acidic conditions for similar systems (Fig. 22) [61]. 

At the time of publication, the shotgun coupling in this synthesis was reported only for the [12]CPP macrocycle. However, upon investigation of what was originally thought to be linear oligomeric byproducts, it was found that the triangular nine-membered macrocycle 60 also forms in similar yields to the [12]CPP precursor (Fig. 27) [42]. 

The "zip-reaction (U. Kramer, 1978, 1979) leads to giant macrocycles. Potassium 3- ami-nopropyl)amide = KAPA ( superbase ) in 1,3-diaminopropane is used to deprotonate amines. The amide anions are highly nucleophilic and may, for example, be used to transam-idate carboxylic amides. If N- 39-atnino-4,8,12,16,20,24,28,32,36-nonaazanonatriacontyl)do-decanolactam is treated with KAPA, the amino groups may be deprotonated and react with the macrocyclic lactam. The most probable reaction is the intramolecular formation of the six-membered ring intermediate indicated below. This intermediate opens spontaneously to produce the azalactam with seventeen atoms in the cycle. This reaction is repeated nine times in the presence of excess KAPA, and the 53-membered macrocycle is formed in reasonable yield. 

In recent years, the variety of useful diazo substrates for asymmetric intramolecular cyclopropanation processes has really expanded. As another example, Charette and Wurz have reported the first example of an intramolecular cyclopropanation involving a-nitro-a-diazo carbonyl compounds.This reaction, catalysed by Rh2[(S)-DOSP]4, led to the formation of nine-membered nitrocyclopropyl lactones in good yields and enantioselectivities with extremely high diastereoselectivities (Scheme 6.17). This novel methodology constituted an efficient entry into chiral functionalised macrocyclic-fused cyclopropane oc-amino acids. 

This reaction was applied to the synthesis of the macrocyclic polyamine alkaloid celacinnine [65] a key step of this synthesis was the conversion of the bicyclic VIII/123 to nine-membered VIII/124, see Scheme VIII/23. 

Indeed, this MCR worked extremely well by simply stirring the three components in trifluoroethanol (TFE) at room temperature. Interestingly, no high-dilution conditions were required for the above transformation. Authors prepared 12-, 15-and 18-membered macrocycles and even nine-membered medium-sized cycles in excellent yields with diastereoselectivities. Two examples were depicted in Scheme 11. Thus, stirring a TFE solution of aziridine aldehyde 29, dipeptide 30 and ferf-butyl isocyanide at room temperature for 4 h afforded a nine-membered cycle 31 in 83% yield. Similarly, a 18-membered cyclopeptide 33 was obtained in 77% yield by the reaction of 29, pentapeptide 32 and ferf-butyl isocyanide. In both examples, the cyclic compounds 31 and 33 were formed with high diastereoselectivities (dr > 20/1). This is intriguing, as Ugi reaction provided generally low to moderate stereoselection when chiral substrates was used as inputs ([66-72] for enantioselective isocyanide-based MCRs, see [73-80]). 

Macrocyclic ligands will be classified, for the purposes of this article, as rings with at least nine members and three or more donor atoms. In a number of cases of unique structural units, elegant descriptive names have developed, which more appropriately describe the macrocyclic shape. Macrocycles will be classified as to donor types and, within the donor types, specific classifications of macrocycles will be noted where applicable. 

Meyers and co-workers" completed the first synthesis of (—)-griseoviridin 1184. In this case, the authors envisioned an unprecedented olefin metathesis reaction of 1269 would construct the macrocycle (Scheme 1.325). Amide bond disconnection of 1269 then led to the key intermediate fragments, an oxazole diene moiety 1270, and the sulfur-containing nine-membered ring lactone 1271. 

The intramolecular transamidation of nine-membered rings has been exploited in the synthesis of macrocycles. Lactam (124), when treated with acid catalyst in refluxing xylene, gave the 13-membered ring (125) (Equation (6)) <92T3775> (see also <80TL3493 . 

---