Macrocyclic acetals analogs

In connection with studies on the ring-opening polymerization of cyclic acetals, we have undertaken investigations on the polymerization of bicyclic acetals, bicyclic oxalactone, and bicyclic oxalactam, which yield polysaccharide analogs, macrocyclic oligoesters, and a hydrophilic polyamide, respectively, some of which can be expected to be useful as novel speciality polymers. The monomers employed in the studies were prepared via synthetic routes presented in Scheme 1, starting from 3,4-dihydro-2H-pyran-2-carbaldehyde (acrolein dimer) I. 

The group of Samuel Danishefsky at the Sloan-Kettering Institute for Cancer Research in New York has also been active in the synthesis of the natural epothilones and biologically active analogs. One of these syntheses also uses the olefin metathesis reaction (not shown). The synthesis in Scheme 13.51 uses an alternative approach to create the macrocycle. One of the key steps is a Suzuki coupling carried out at step H-(l,2) between a vinylborane and vinyl iodide. The macrocyclization is an aldol addition reaction at step H-4. The enolate of the acetate adds to the aldehyde, creating the C(2)-C(3) bond of the macrolactone and also establishing the stereocenter at C-3. 

The complexation properties of the macrocyclic, spider-like tetraaza-tetraace-tate ligand DOTA were found by Desreux to be very unique [45]. The stability constants of the complexes Ln(DOTA)- are very high and both the formation and dissociation rates are unusually low. The behavior of the DOTA- analogous ligands containing at least three acetate and three or four methylene-phospho-nate or methylene-phosphinate groups is very similar, and a number of new derivatives have been synthesized and investigated in order to develop new CAs. 

Michael reaction of macrocyclic ketene silyl acetals or a-enones occurs smoothly under electron-transfer conditions whereas the reaction of 6-membered analogs is more sluggish, indicating the importance of ring flexibility to enable the a,/8-carbon-carbon bonds of both reaction components to rotate when the radical species are generated [72c]. 

The 14-membered macrocyclic ring of (-)-galbonolide B was formed utilizing a novel macro-Dieckmann cyclization which was developed in the laboratory of B. Tse. In order to bring about the desired macrolactonization, the secondary acetate was treated with LiHMDS in refluxing THF under high-dilution conditions to afford the desired lactone in 75% yield. It is important to note, however, that the analogous secondary propionate failed to cyclize under identical conditions. 

A fermentation study [18] using Streptomyces avermitilis culture 5192 and [1- C] acetate and [1- C] propionate precursors, followed by NMR analysis of the products, established the incorporation of seven acetate and five propionate units into the macrocycle. Carbon 25 and its substituents were shown to be derived from L-isoleucine and l-valine following deamination and conversion into the analogs carboxylic acids. That the C-25 substituent is derived from a... 

A series of macrocyclic compoimds possessing a unique dispiroacetal l,7,9-trioxadispiro[5.1.5.2]pentadecane and a bicyclic acetal 6,8-dioxabi cyclo[ 3.2.1] octane concomitant with a spirocycHc imine part were isolated from marine bivalves. Pinnatoxin A (104) was isolated from the Okinawan bivalve Pinna muricata [50,51] and pinnatoxins B (105) and C (106) [52], and pteriatoxins A-C (107-109) were isolated from Pinna penguin [53]. These compounds seem to be responsible for Pinna shellfish poisonings in China and Japan, as Ca " activators [54]. In addition, analogous compounds without the bicyclic acetal, spiroHdes A-E (110-114), were produced by the dinoflagellate Alexandrium ostenfeldii [55,56]. 

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