<i>p</i>-Anisyloxymethyl Group, a Novel Oxidatively Removable Acetal Type OH-Protecting Group

Yoshio, Masaki; Iwata, Ikuhiro; Mukai, I.; Oda, Hirohisa; Nagashima, Hiromu

doi:10.1246/cl.1989.659

Cited by 13 publications

(4 citation statements)

References 7 publications

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“…Of all the attempted protections or derivatizations of the tertiary alcohol in 4 , only base-promoted reactions with alkoxymethyl chlorides have worked well. To the extent that crystallinity might be expected to be related to the melting point of the alkoxy group employed, 4-phenylphenol (mp 165−167 °C) was selected for incorporation into a new protecting group . The previously unknown 1-(chloromethoxy)-4-phenylbenzene (POMCl) was synthesized in 74% yield from p -chlorothiophenol according to a literature method as shown below (Scheme ) …”

Section: Resultsmentioning

confidence: 99%

A Convergent, Scalable Synthesis of HIV Protease Inhibitor PNU-140690

et al. 1998

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PNU-140690, an inhibitor of the HIV protease enzyme undergoing clinical evalution as a chemotherapeutic agent for treatment of AIDS, was synthesized by a convergent approach amenable to large-scale preparation in a pilot plant environment. The key step is the aldol addition of nitroaromatic ester (+)-8 to aldehyde 19e. The two stereocenters present in the target molecule were each set independently by resolution of enantiomers. Intermediates along the synthetic routes were chosen to maximize opportunities for isolation and purification by crystallization.

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Section: Resultsmentioning

confidence: 99%

A Convergent, Scalable Synthesis of HIV Protease Inhibitor PNU-140690

et al. 1998

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“…Cleavage of the double bond under classical conditions (Scheme ), using osmium tetroxide and sodium periodate, gave an aldehyde ( 31 → 32 , 73%), and that was reduced with sodium borohydride (96%) to the expected primary alcohol. Finally, the hydroxyl group was protected as its p -anisyloxymethyl ether ( 33 → 34 , 91%).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of (±)-Calicheamicinone by Two Methods

Clive

Tao

et al. 1998

J. Am. Chem. Soc.

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Ketene acetal 25 was converted into silyl enol ether 20, which underwent a Diels−Alder reaction with methyl (E)-3-nitropropenoate to afford ketone 27. This was converted by two routes into (±)-calicheamicinone (1). In the first, modification of the nitro, ester, and allyl substituents gave ketone 38, which reacted stereoselectively with cerium trimethylsilylacetylide to place the acetylene unit syn to the nitrogen function (38 → 39). Further elaboration took the route as far as aldehyde 42. A slightly different series of reactions served to convert ketone 27 into tricyclic ketone 43. This also reacted with cerium trimethylsilylacetylide, but in the opposite stereochemical sense to 38, so as to place the acetylene unit anti to the nitrogen function (43 → 50). Further elaboration took this second route as far as lactone 44. Both 42 and 44 serve as advanced intermediates for the synthesis of (±)-calicheamicinone. The monoacetylenic aldehyde 42 reacted stereoselectively with cerium trimethylsilylacetylide to give the bis(acetylene) 53 as the major product. This was elaborated into lactone 60, which was desaturated (60 → 68) and methoxycarbonylated on nitrogen. The acetylenic silyl groups were then removed, so as to generate syn bis(acetylene) 72, and the terminal acetylenic hydrogens were replaced by iodine. The resulting diiodide 81 formed the cyclic enediyne 82 on reaction with (Z)-1,2-bis(trimethylstannyl)ethene in the presence of (Ph3P)4Pd, and the enediyne was converted into (±)-calicheamicinone. syn-Bis(acetylene) 72 was also synthesized from the other advanced intermediate (lactone 44), using, as a key step, free radical bromination of the derived unsaturated lactone 77. The resulting bromo lactones 78 were converted into an aldehyde ester 79, and this reacted stereoselectively with cerium trimethylsilylacetylide to give 80, convertible by the action of TBAF into 72.

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“…3,7,11-Trimethyl-2 E ,6 E -dodecadienyl Benzyl Ether (50) and 6-Isoamyl-3,7-dimethyl-2 E ,7-octadienyl Benzyl Ether (51). Alcohol 48 (510 mg, 1.96 mmol) in THF (20 mL) at 0 °C was treated with pyridine (0.05 mL, 0.62 mmol) and PBr 3 (0.10 mL, 1.05 mmol). The resulting suspension was stirred for 1 h and then washed with NaHCO 3 .…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Farnesol Analogues through Cu(I)-Mediated Displacements of Allylic THP Ethers by Grignard Reagents

Mechelke

Wiemer

1999

J. Org. Chem.

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The synthesis of a family of farnesol analogues, incorporating aromatic rings, has been achieved in high yields through the development of a regioselective coupling of allylic tetrahydropyranyl ethers with organometallic reagents. The allylic THP group is displaced readily by Grignard reagents in the presence of Cu(I) halides but is stable in the absence of added copper. Thus, an allylic THP group can fulfill its traditional role as a protecting group or serve as a leaving group depending on reaction conditions. An improved synthesis of (2E,6E)-10,11-dihydrofarnesol also has been accomplished using this methodology, and some preliminary studies on the reactivity and regioselectivity of THP ether displacements were conducted. The farnesol analogues reported herein may be useful probes of the importance of nonbonding interactions in enzymatic recognition of the farnesyl chain and allow development of more potent competitive inhibitors of enzymes such as farnesyl protein transferase.

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p-Anisyloxymethyl Group, a Novel Oxidatively Removable Acetal Type OH-Protecting Group

Abstract: Protection of various types of alcohols with p-anisyloxymethyl (p-AOM) chloride gave the corresponding p-AOM ethers which were deprotected with ceric ammonium nitrate efficiently. Chemoselective removal either of p-AOM group or of tetrahydropyranyl group is also reported.

Cited by 13 publications

References 7 publications

A Convergent, Scalable Synthesis of HIV Protease Inhibitor PNU-140690

A Convergent, Scalable Synthesis of HIV Protease Inhibitor PNU-140690

Synthesis of (±)-Calicheamicinone by Two Methods

Synthesis of Farnesol Analogues through Cu(I)-Mediated Displacements of Allylic THP Ethers by Grignard Reagents

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