Cyclopropanes Aminocyclopropanes

Karthikeyan S, Q Zhou, Z Zhao, C-L Kao, Z Tao, H Robinson, H-w Liu, H Zhang (2004) Structural analysis of Pseudomonas 1-aminocyclopropane-l-carboxylate deaminase complexes insight into the mechanism of a unique pyridoxal-5 -phosphate dependent cyclopropane ring-opening reaction. Biochemistry 43 13328-13339. 

This version of the Curtius rearrangement has been applied to the synthesis of amino acid analogs and structures containing amino acids. Several m-2-aminocyclopropane carboxylate esters were prepared by selective hydrolysis of cyclopropane-1,2-dicarboxylates, followed by reaction with DPPA.267... 

Diacylmethylene)cyclopropanes (34) generated from the corresponding aminocyclopropanes 33 and acetylchloride (Scheme 6) are highly reactive intermediates and can be trapped by dienes such as 2,3-dimethylbutadiene (35), pentadiene 36 and isoprene (37) yielding the Diels-Alder products 38-40 [14]... 

A few natural products which contain the cyclopropyl ring have been synthesized through metal catalysed cyclopropanation using dicarbonyl diazomethanes. ( )-Cycloeudesmol 63, isolated from marine alga Chondria oppositiclada, was synthesized via a sequence involving a copper catalysed cyclopropanation of a-diazo-/8-ketoester 61 to give the key intermediate 62 (equation 73)1 7,108. Similarly, the bicyclo[3.1.0]hexane derivative 65 was synthesized from the corresponding a-diazo-/8-ketoester 64 via the catalytic method and was converted into ( )-trinoranastreptene 66 (equation 74)109. Intramolecular cyclopropanation of -diazo-/i-ketoesters 67 results in lactones 68 which are precursors to 1-aminocyclopropane-l-carboxylic acids 69 (equation 75)110. 

Photochemical Fe(CO)5-induced rearrangement of silylated allyl amine 9 gave N-silylated enamine 1015, which on subsequent Cu-catalyzed cyclopropanation by methyl diazoacetate afforded cyclopropane derivative 11. The use of an optically active catalyst gave an asymmetric induction of 56% ee for the cis isomer and 20% ee for the trans isomer. Further acid-induced ring cleavage afforded the -formyl ester 12, whereas reduction and desilylation produced aminocyclopropane carboxylic acid 13 (equation 2). 

In contrast to the restricted occurrence of the secondary metabolites mentioned previously, all plants contain 1-amino-cyclopropane-l-carboxylic acid. This amino acid is the precursor of ethylene. In the course of the bios)mthesis of this gaseous phytohormone, 1-aminocyclopropane-l-carboxylic acid is oxidized and decomposed to yield ethylene, HCN, CO2 and water (John, 1997). 

During the reaction of the doubly activated allyl halides with primary and secondary amines no 2-amino-substituted cyclopropane derivatives could be isolated, but instead ring-opened products are formed. Primary amines give rise to the formation of aldimines (332) while secondary amines afford formally substitution products (333) . The formation of these products can be explained by ring cleavage of non-isolable electrophilic 2-aminocyclopropanes (331) as outlined in equation 104. 

Most of the compounds cited in this introductory section are produced in metabolic processes where the cyclopropane-containing metabolite appears to be the stable end product or secondary product with as yet unobvious metabolic function. However, this is not the case in at least two types of systems, in which cyclopropyl species are key and necessary intermediate structures in high flux metabolic pathways. The first example is the squalene (76) and phytoene (88) biosynthesis where presqualene pyrophosphate (77) and prephytoene pyrophosphate (89) are obligate cyclopropanoid intermediates in the net head-to-head condensations of two farnesyl pyrophosphate (73) or two geranylgeranyl pyrophosphate (66) molecules respectively. The second example is in plant hormone metabolism where C(3) and C(4) of the amino acid methionine are excised as the simple hormone ethylene via intermediacy of 1-aminocyclopropane-l-carboxylic acid (9). Both examples will be discussed in detail in the Section II. 

In this section we analyze information about metabolic cleavage or breakdown of cyclopropane rings in three instances the biosynthesis of irregular monoterpenes, the ringopening of cycloartenol (20) derivatives, and the metabolic opening of 1-aminocyclopropane-1-carboxylic acid (ACPC) (9) by two quite distinct fragmentation routes. We will not explicitly discuss the processing of presqualene pyrophosphate (77) and prephytoene pyrophosphate (89) to squalene (76) and phytoene (88) respectively, since those transformations have already been dealt with in Section II. 

Aminocyclopropanes (1) are typical representatives of the family of donor-substituted cyclopropanes. The combination of an amino moiety with the cyclopropane ring is not only of theoretical interest for possible donor-acceptor interactions, but is also the origin of an easy nucleophilic substitution of a group X in (1) or a ring-opening reaction. Intermediates 2 and 3 represent these two types of reactions according to the sequence 1 - 3 an aminocyclopropane is to be regarded as a homoenamine species. 

The following review covers especially the synthesis of aminocyclopropanes it deals with compounds in which a NR R moiety (R R heteroatom) is directly bonded to the three-membered ring. Cyclopropanes with other nitrogen functional groups are not included. Literature was considered until the end of 1984 the text was supplemented in October 1985. A very short review on aminocyclopropane chemistry appeared in 1974 by Gibson and DePuy Wasserman and coworkers surveyed some aminocyclopropane compounds derived from cyclopropanones. ... 

The acyl azide - isocyanate rearrangement is known to proceed stereospecifically with retention of both optical and geometrical (cis-tranSy endo-exo) configuration. Thus, optically active aminocyclopropanes were obtained from optically active cyclopropane carboxylic acid derivatives A lot of exo-amiobicyclo[n.l.O]alkanes or... 

Strongly basic nucleophiles such as an amide ion allowed a nucleophilic substitution via an elimination-addition mechanism of cyclopropane derivatives possessing an acidic hydrogen atom " ". Aminocyclopropanes 121 and 122 were synthesized in this manner from the corresponding halogenocyclopropanes " (equations 28 and 29). 

Aminocyclopropanes have also been prepared from metalated cyclopropanes 123 and... 

The cyclothymidin isomers (162) could be separated by chromatography. Interaction of 158 with hydroxide or sodium borohydride led to the aminocyclopropanes 159 and 160. An analogous cyclopropanation was performed with 4-pyrimidones , pyridinediones or oxopyridopyrimidines . ... 

Photolysis of aminopyrrolinones (329) also led to aminocyclopropane derivatives (330) which were transferred into the urea derivatives (331) (equation 79). Cyclopropanes... 

The aminocyclopropane derivative 374 and the propellane 372 were obtained, each in 26 % yield, by photocycloaddition of 370 and ethylene in acetone . Diradicals 371 and 373 were suggested as intermediates in the photoreaction (equation 90). The use of isobutene or 2,3-dimethyl-2-butene instead of ethylene gave no cyclopropane product . 

Theroretical considerations, spectroscopic properties, chemical reactions and the biochemistry of aminocyclopropanes are discussed together with those of other cyclopropane... 

Cyclopropylamine (77) could be oxidized to nitrosocyclopropane (432) by oxygen difluoride or m-chloroperbenzoic acid (equation 106). Azo compounds 433 and 435 were obtained by oxidation of 434 by IF5 (equation 107) or condensation of 77 with a nitroso compound (equation 106). Interconversions of an aminocyclopropane into an isocyano or azido cyclopropane are described, for example, in Refs 105,479-481,515,516 and Refs 89, 461, 517, respectively. For formation of an N-cyclopropyl iminiophos-phorane see Ref. 518. Nitrosation of iV-cyclopropylurea derivatives was usually performed... 

Opening of the vicinal carbon-carbon bond in aminocyclopropane derivatives was achieved by oxidation with various reagents, e.g. Pb(OAc)4 , NaOCP r-BuOCpi Cu2 /0 Cu/0 0s04/0 K3Fe(CN) Cu or fiv/Oa/sens., anodic oxidation Oxidation with halogenating reagents such as NaOCl or t-BuOCl proceeds via N-chloro compounds (see equation 105), which opened the C(l)-C(2) cyclopropane bond when the cyclopropylamine had one substituent at the iV-atom (e.g. 489- 490 equation 125) or a phenyl moiety in the C(2) position. 

In general the less stable bond of a cyclopropane ring is cleaved by a hydrogenolysis reaction, e.g. Ref. 549. In aminocyclopropane derivatives the C(2)-C(3) bond proved to be... 

A primary amino function in aminocyclopropanes (413) can be removed easily by diazotation (for a review see Ref. 594). In the absence of any steric restrictions, displacement of the diazonium group led mainly to ring-opened allylic substitution products (579)3.4.11.53.84.86.144,147.595 (equation 150). Substituted cyclopropanes (580) are obtained only to a very small amount they were formed mainly (> 92 %) with inversion of configuration (see also Ref. 218). 

In 1971 Burger reviewed biochemical activities of cyclopropane compounds almost half of this review deals with aminocyclopropane derivatives. In 1975, a similar review on the same topic was published by Otto. ... 

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