Closed-ring analogues

The three closed ring group of substituents mentioned in the pyr-T recipe have also been described with this 5,6-methylenedioxy ring substitution. These could be named 5,6-MDO-pyr-T (the pyrrolidine analogue, mp 110-112 °C), 5,6-MDO-pip-T (the piperidine analogue, mp ISO-152 °C) and 5,6-MDO-mor-T (the morpholine analogue, mp 117-119 °C). To my knowledge, none of these has ever been put into man. 

These reactions occur well without the enzyme (Chapter 36) but the enzyme accelerates this reaction by ah out a 106 increase in rate. There is no acid or base catalysis and we may suppose that the enzyme binds the transition state better than it binds the starting materials. We know this to be the case, because close structural analogues of the six-m embered ring transition state also bind to the enzyme and stop it working. An example is shown alongside—a compound that resembles the transition stale but can t react. 

Photoelectron spectroscopic data, marked (PE) , are from Ref. [20, 25]. The numbers in boldface type are from X-ray crystallography [12, 26]. For discussion of the conformations of the six-membered ring hydrazines, see Ref. [27]. Entries in parentheses are for data taken on very close structural analogues to compounds that have experimental data, for which we believe the 9 values given also apply. 

Kalinin, A.V., Chauder, B.A., Rakhit, S. and Snieckus, V. (2003) seco-C/D ring analogues of ergot alkaloids. Synthesis via intramolecular Heck and ring-closing metathesis reactions. Org. Lett., 5, 3519-21. 

Any heterocycle containing the OCH=CH moiety can in principle extrude the superfluous fragment and form oxirene, as illustrated for a five-membered ring in Scheme 105. Probably the most propitious AB fragment would be nitrogen, but the required 1,2,3-oxadiazole (123) is unknown (see Chapter 4.21), probably because of ready valence tautomerization to diazoethanal (Scheme 106) (this approach has been spectacularly successful with the sulfur analogue of (2) (8UA486)). The use of (123) as an oxirene precursor is thus closely linked to the important diazo ketone decompositions discussed in Section 5.05.6.3.4(f). 

Two closely related indoles fused to an additional saturated ring have been described as CNS agents. The first of these is obtained in straightforward manner by Fischer indole condensation of functionalized cyclohexanone 0 with phenyl hydrazine (19). The product, cyclindole (21) shows antidepressant activity. The fluorinated analogue flucindole (26) can be prepared by the same scheme. An alternate route starting from a somewhat more readily available intermediate involves as the first step Fischer condensation of substituted phenyl hydrazine with 4-hydroxycyclohexanone (23). The resulting alcohol (24) is then converted to its tosylate (25). Displacement by means of dimethyl amine leads to the antipsychotic agent flucindole (26). ... 

To date, all saturated and unsaturated three- and larger-membered ring sulfones and sulfoxides (e.g., thiirane (3), thiirene (4), thietane (5), thiete (6), dithietane (7), thiolane (8), thiolene (9), thiane (10), thiene (11), dithiane (12), thiepane (13), thiocane (14), and their unsaturated analogues as well as isomers and closely-related systems) have been synthesized and their chemistry well-established. 

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