Tethered substrates preparation

The inverse-electron-demand DAR described above can also be applied to the synthesis of terminally modified RNA transcripts. A norbornene-derivatized initiator nucleotide was synthesized, efficiently incorporated into RNA, and used for the mild preparation of RNA-peptide conjugates [19a]. A selection of tethered substrates is shown in Figure 18.5. 

Scheme 16.30 provides an easy visualization of the dipolarophile placement in the starting material for each of the four modes of the intramolecular [3 + 2] cycloadditions. Thus, to prepare a C(3)-tethered substrate 114 for the spiro mode of the [3 + 2] cycloaddition, the dipolarophile must be attached to the a-carbon of the nitroalkene 112. Alternatively, to prepare a C(4)-tethered substrate 117 for the fused... 

Other early studies of RRCM apphcations in our labs were carried out by Danielson [9], Tennakoon [4, 10], Wang [4, 11], and JeHfey [4, 12]. RCM of the silicon-tethered substrates 25 and 28 to give the hindered (2)-trisubstituted alkene, an intermediate for use in our synthesis of peloruside A (29), was successful in both cases (Scheme 9.6) [5, 10]. However, it was difficult to prepare 25 in high diastereomeric purity. More specifically, the two enantiomers of the secondary alcohol precursor ( )-24 were barely discriminated by several Upases that we examined. By contrast, citroneUene-derived alcohol 27, a 1 1 mixture of epimers at C15, could be kinetically resolved quite efficiently. Thus, the relay tether served an auxiliary but nonetheless important role, merely because of its size. 

Swager et al. prepared conjugated polymers with tethered rotaxane groups [76]. As a substrate, a rotaxane containing a diiodobiphenyl unit was synthesized for this purpose. Polymerization via microwave-assisted Sono-... 

The artificial lipid bilayer is often prepared via the vesicle-fusion method [8]. In the vesicle fusion process, immersing a solid substrate in a vesicle dispersion solution induces adsorption and rupture of the vesicles on the substrate, which yields a planar and continuous lipid bilayer structure (Figure 13.1) [9]. The Langmuir-Blodgett transfer process is also a useful method [10]. These artificial lipid bilayers can support various biomolecules [11-16]. However, we have to take care because some transmembrane proteins incorporated in these artificial lipid bilayers interact directly with the substrate surface due to a lack of sufficient space between the bilayer and the substrate. This alters the native properties of the proteins and prohibits free diffusion in the lipid bilayer [17[. To avoid this undesirable situation, polymer-supported bilayers [7, 18, 19] or tethered bilayers [20, 21] are used. 

Complex 7-AI2O3/PTA/ (/< ./< )-(Mc-DuPHOS)Rh(COD) 1 (1) was prepared and tested in the hydrogenation of the prochiral substrate methyl-2-acetamidoacrylate (MAA). After full conversion, the products were separated from the catalyst and analyzed for Rh and W content and product selectivity. The catalyst was re-used three times. Analytical results show no rhodium leaching is observed. Complex 1 maintains its activity and selectivity in each successive run. The first three runs show tungsten (W) leaching but after that no more W is detectable. The leached W comes from the excess of PTA on alumina. The selectivity of both tethered and non-tethered forms gave the product in 94% ee. 

Lautens and coworkers [9] ultimately used this approach to prepare a multitude of different polyheterocyclic ring systems 4-29, using 4-20 and 4-28 as substrates (Table 4.1). Unsymmetrical tethered bisfurans and acetylene dicarboxyclic acid derivatives have also been used in this domino process to allow the formation of three new rings with up to six stereogenic centers. 

Printable elements, especially those prepared by top-down methods, are often prepared such that they are attached to the mother substrate by tethers and anchoring structures that keep the otherwise freestanding elements in place. To separate elements from the mother substrate in the retrieval step, stamps must successfully break these tethers, which are typically composed of the same inorganic material as the elements. This process often requires careful design of the elements and tethers such that the elements separate by well-controlled and reliable fracture. Simple fracture theory63 points to several important factors that lead to easy fracture, notably the presence of cracks in the inorganic material and the geometry of those cracks. 

Several investigators have studied intramolecular Heck reactions on alkene-tethered haloindoles. Black prepared several l-allyl-7-bromoindoles and found that they undergo cyclization in the presence of palladium as shown for 242 to 243 [267]. Although this new synthesis of pyrroloquinolines is reasonably general, some of the products are unstable. Substrate 242 was prepared by bromination of 4,6-dimethoxy-2,3-diphenylindole (92%) and //-alkylation. 

Over the past several years, Mascarenas and co-workers (150-153) utilized the oxidopyrylium ion with variously hetero-substituted olefin tethers. Mascarenas has used this methodology in tandem with a Diels-Alder reaction to prepare tricyclic cycloheptanoid substrates. Further, Mascarenas and co-workers (154—156) achieved the synthesis of optically active oxabicyclic[3.2.1]octane derivatives through the addition of a homochiral p-tolylsulfinyl group substituted at the olefin tether. The Mascarenas group has also used this methodology to prepare the THF portion of ( )-nemorensic acid via oxidative cleavage of the substituted a-hydroxyketone moiety (157) (Scheme 4.78). 

Fused ring heterocycles, prepared by cyclization of substrates with a tethered nitrogen nucleophile, have been used in the synthesis of amino sugars and aminocyclitols. The examples shown in Table 28 make use of imidate-type functionality (equation 101) to insure nucleophilic attack by nitrogen. The bro-mocyclization of N,W-dialkylaminomethyl ethers of 2-cyclohexen-l-ol to form bicyclic oxazolidine derivatives has been reported also.228b... 

By using a different length of tether between the aldehyde and the dienophile moiety in the aromatic or hetero-aromatic substrates various different highly diversified heterocyclic compounds can be prepared. Thus, reaction of 19 and 15b led to 20 containing a new 5,6-ring system, whereas reaction of 21 and 15b gave 22 with a 7,6-ring system (Scheme 5.5) [11],... 

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