Reaction mechanisms : Part (ii) Pericyclic reactions

Tantillo, Dean J.

doi:10.1039/b518097j

Cited by 10 publications

(3 citation statements)

References 64 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The absence of an activation barrier for the cyclization 7 Ǟ (Z)-2 can be explained with dative bonding theory (Hodgen et al, 2003) and, formally, with the theory of pericyclic reactions (Tantillo, 2006;Morgan, 2005). In the dative bonding model, the new C-N -bond is formed by shifting the imine's N-lone pair toward the central C-atom of the keteneimine.…”

Section: Uncatalyzed Cyclization Of the Monocyclic Hcn-pentamermentioning

confidence: 99%

Adenine Synthesis in Interstellar Space: Mechanisms of Prebiotic Pyrimidine-Ring Formation of Monocyclic HCN-Pentamers

et al. 2007

View full text Add to dashboard Cite

The question whether the nucleobases can be synthesized in interstellar space is of fundamental significance in considerations of the origin of life. Adenine is formally the HCN pentamer, and experiments have demonstrated that adenine is formed under certain conditions by HCN pentamerization in gas, liquid, and condensed phases. Most mechanistic proposals invoke the intermediacy of the HCN tetramer AICN (4), and it is thought that adenine synthesis is completed by addition of the 5(th) HCN to 4 to form amidine 5 and subsequent pyrimidine cyclization. In this context, we have been studying the mechanism for prebiotic pyrimidine-ring formation of monocyclic HCN-pentamers with ab initio electronic structure theory. The calculations model gas phase chemistry, and the results primarily inform discussions of adenine synthesis in interstellar space. Purine formation requires tautomerization of 5 to the conjugated amidine 6 (via hydrogen-tunneling, thermally with H(+) -catalysis, or by photolysis) or to keteneimine 7 (by photolysis). It was found that 5-(N'-formamidinyl)-1H-imidazole-4-carbonitrile (6) can serve as a substrate for proton-catalyzed purine formation under photolytic conditions and N-(4-(iminomethylene)-1H-imidazol-5(4H)-ylidene)formamidine (7) can serve as a substrate for uncatalyzed purine formation under photolytic conditions. The absence of any sizeable activation barrier for the cyclization of 7 to the (Z)-imino form of 9H-adenine (Z)-2 is quite remarkable, and it is this feature that allows for the formation of the purine skeleton from 7 without any further activation.

show abstract

Section: Uncatalyzed Cyclization Of the Monocyclic Hcn-pentamermentioning

confidence: 99%

Adenine Synthesis in Interstellar Space: Mechanisms of Prebiotic Pyrimidine-Ring Formation of Monocyclic HCN-Pentamers

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Electrocyclization reactions offer a powerful ring-forming strategy, with the possibility for simultaneous creation of one or two new stereocenters . We have recently investigated the 4π Nazarov electrocyclizations of cross-conjugated dienones in which one of the alkene units is encased within an enantiomerically pure bridged bicyclic skeleton. , In these studies, high diastereoselectivity for cyclization from the exo face of the bicyclic system was seen in most cases; however, bicyclo[3.2.1]octadiene systems such as 1 displayed complete endo selectivity in their cyclizations (Scheme ).…”

mentioning

confidence: 99%

Highly Stereoselective 6π Electrocyclization of Bridged Bicyclic 1,3,5-Trienes

Benson

West

2007

Org. Lett.

View full text Add to dashboard Cite

Conjugated 1,3,5-hexatrienes encased in bridged bicyclic skeletons are prepared by cross-coupling followed by half-reduction of the resulting dienynes. The trienes undergo 6pi electrocyclization at an ambient or elevated temperature to furnish complex, polycyclic cyclohexadienes. In all cases, complete selectivity in favor of cyclization from the exo face of the bridged bicyclic system was seen, in contrast to the corresponding 4pi Nazarov cyclizations.

show abstract

“…The photosensitive metal-free CO-RMs rely on the ability of photons to cleave C–C bonds in certain structures. For prodrugs that would release CO under physiological conditions, we thought about using pericyclic reactions, which are well-known for the ability to easily break and form C–C bond under mild conditions . Specifically, our design strategy relies on the ability of norbornadien-7-ones to undergo facile cheletropic reaction to extrude CO under mild conditions .…”

Section: Introductionmentioning

confidence: 99%

Strategies toward Organic Carbon Monoxide Prodrugs

2018

View full text Add to dashboard Cite

Carbon monoxide is widely acknowledged as an important gasotransmitter in the mammalian system with importance on par with that of nitric oxide. It has also been firmly established as a potential therapeutic agent with a wide range of indications including organ transplantation, cancer, bacterial infection, and inflammation-related conditions such as colitis and sepsis. One major issue in developing CO based therapeutics is its delivery in a pharmaceutically acceptable form. Currently, there are generally five forms of deliveries: inhaled CO, photosensitive CO-releasing molecules, encapsulated CO, CO dissolved in drinks, and molecules that would release CO under physiological conditions without the need for light. For over a decade, the last category only included metal-based CO releasing molecules. What had been missing were organic CO prodrugs, which release CO under physiological conditions with tunable rates and in response to various exogenous and endogenous triggers such as water, chemical reagents, esterase, ROS, and changes in pH. This Account describes our work in this area as well as the demonstration for these organic prodrugs to recapitulate CO's pharmacological effects both in vitro and in vivo. Generally, two categories of CO prodrugs have been developed in our lab. Both can be considered as precursors of norbornadien-7-ones, which readily undergo cheletropic reaction under very mild conditions to extrude CO. The first category of CO prodrugs capitalizes on the inter- and intramolecular inverse electron demand Diels-Alder (DA) reaction to trigger CO release under physiological conditions. As for the bimolecular CO prodrugs, we proposed a new concept of "enrichment triggered CO release" by conjugating both components with a mitochondria-targeting moiety to achieve targeted CO delivery with improved biological outcomes in vitro and in vivo. As for the unimolecular CO prodrugs, the release half-lives can be readily tuned from minutes to days by varying the substituents on the dienone ring, the tethering linker, and the alkyne. Some significant structure-release rates relationships (SRRs) have been unveiled. An esterase-activated CO prodrug and a cascade prodrug system for co-delivery of CO and another payload have also been devised using such an intramolecular click and release strategy. The second category of CO prodrugs leverage on an elimination reaction to generate norbornadien-7-ones for CO release from norborn-2-en-7-ones. In the case of pH-sensitive ones, the CO release is triggered by β-elimination, and the release rate can be quantitatively predicted using the Hammett constant of the substituents on the leaving group. The ROS-activated ones take advantage of ROS-induced selenoxide elimination to achieve targeted CO delivery to disease sites with elevated ROS level. We strongly believe that these CO prodrugs could serve as powerful tools for CO-associated biological studies and are promising candidates for ultimate clinical applications.

show abstract

Reaction mechanisms : Part (ii) Pericyclic reactions

Cited by 10 publications

References 64 publications

Adenine Synthesis in Interstellar Space: Mechanisms of Prebiotic Pyrimidine-Ring Formation of Monocyclic HCN-Pentamers

Adenine Synthesis in Interstellar Space: Mechanisms of Prebiotic Pyrimidine-Ring Formation of Monocyclic HCN-Pentamers

Highly Stereoselective 6π Electrocyclization of Bridged Bicyclic 1,3,5-Trienes

Strategies toward Organic Carbon Monoxide Prodrugs

Contact Info

Product

Resources

About