OTBS Yxs
conditions a NaBH4, MeOH-15 C b allylMgBr, THF, -78 C c allylTMS, BF3-Et20, DCM, 0 C 96 d H2, Pd C, EtOH 100 e Et3SiH, BF3 Et20, DCM thylsilane in the presence of boron trifluoride etherate affords lactam 787 96 4 . Depro-tection with CAN and palladium black, mesylation, and cyclization yields the bicyclic amide 788 in good yield. Desilylation occurs readily under acidic conditions, and a final lithium aluminum hydride reduction of the amide affords 789, which was determined to have a 92 de at...
Info Keg
conditions a Swern O , -60 C b CF3CH20 2P 0 CH2C00Me 18-crown-6, KN TMS 2, THF.-78 C 90 2 steps c 1N HCI, MeOH d TBPSCI, imidazole, DCM 94 2 steps e TsOH, benzene f DIBAL, toluene-78 C g CSA, MeOH 86 3 steps h DDQ, DCM-MeOH, buffer 97 i MCPBA, radical scavenger, DCM, reflux 74 cytotoxic activity. Tosylation of 925 followed by copper-catalyzed addition of allylmagne-sium chloride provides the olefin 929 in 78 overall yield. This is deprotected, selectively tosylated at the primary hydroxyl...
I Ugy
The central ring 777 of elaiophylin, a macrodiolide antibiotic isolated from fungi, is synthesized from iS -malic acid via triol 767 as shown in Scheme 111 167 . Since the ring is C2-symmetric, only half the molecule need be prepared. Triol 767 originates from lithium aluminum hydride reduction of alkylated malate 225a. Acetal formation with benzaldehyde furnishes 768 86 , which is further transformed into amide 771 via the nitrile 770. Hydrogenolysis of the acetal leads to a diol that is...
Info Ipg
c LiAIH4, THF 92 d Boc20, Et3N, DCM 89 e Cr CO 6, Bu20, THF 63 f HCOOH, 20 C, 5 h 95 g 3,4- MeO 2C6H3CH2Br, DCM 36 h HBF4 OMe2, DCM 67 i air 98
Chemical Reactions Of Hydroxy Acids
conditions a PhCH2ONH2, THF, 0 C, 3 h 69 b Ac20, 90 C, 3 h 94 c p-TsOH, MeOH, reflux, 5 h 85 d H2, Pd C, EtOH The anhydride of unprotected tartaric acid is difficult to prepare and almost impossible to isolate. Stable anhydrides such as 720a and 720b, where the hydroxy groups are esterified, do not permit reactions with alcohols in the absence of ester hydrolysis. The ability of a tri-chloroacetate protecting group to activate the anhydride towards nucleophilic attack, while proving less labile...
Info Wkc
454 with dimethylamine furnishes 7 -recipavrin with nearly complete inversion of the asymmetric center 96 ee . S -Recipavrin is prepared from 454 by two consecutive inversion reactions, where the tosylate is first converted to bromide 455 and the bromide ion is displaced with dimethylamine 84 ee . Treatment of 456 with bromoethane gives the corresponding enantiomeric quaternary ammonium salt, emepronium bromide, which is an anticholinergic agent with effects similar to atropine.
Info Vtf
conditions a LiAIH4-AICI3 1 1 , Et20-DCM b Me2C OMe 2, p-TsOH c n-C16H33OMs, KH, PhH 88 or n-C18H37OMs, KH, PhH 94 d 2N HCI, THF e Pb OAc 4, PhH, then NaBH4, MeOH The synthesis of the 2-O-methyl analogue 359, which exhibits growth-inhibitory activity on cultured myeloid leukemia cells, demonstrates the flexibility of this methodology. Alkylation of 353 followed by reductive debenzylation and alkylation of the secondary hydroxy group with methyl iodide provides...
HO Gjc
conditions a p-MeOC6H4CH OMe 2, TsOH, DMF 99 b NaBH4, LiCI, EtOH 100 c BH3 THF, reflux 94 d 3-pentanone, TsOH, THF 89 e Swern O f Ph3PCH2 CH2 12MeBr, Ph Li, toluene,-30 C then MeOH- water 62 2 steps g 2 aq. H2S04, MeOH 93 h TBSCI, Et3N, DMAP, DCM 91 i MsCI, pyridine, 0 C j NaN3, 18-crown-6, DMF, 75 C 87 k DDQ, DCM-water 87 I Bu4NF, THF 94 Inhibitors of a-glucosidases are useful drugs for controlling non-insulin-dependent diabetes mellitus by preventing a rise in blood glucose. They are also...
Info Fvp
conditions a LDA, THF, -78 C, then 658 b CH3I, MeOH, -15 C c DBU, acetone Similar types of compounds 674 are available through a direct reaction of 658 with the vinylcarbonyl compounds 673 in the presence of a catalytic amount of DABCO 10 mol 202 . For both derivatives, the anti isomer 674 predominates to approximately the same extent 70 30 . In the case of enone 673 R CH3 , using l-azabicyclo 2.2.2 octan-3-ol instead of DABCO as the catalyst increases the yield of the reaction from 54 to 80 ....
Info Aus
coupling step is accomplished by displacement of the mesylate 115, generated from acetonide 109, with phenol 114. Mesylate 115 is readily prepared from 109 by treatment with metha-nesulfonyl chloride and pyridine in methylene chloride 90 yield . Other leaving groups such as tosylate or iodide were investigated but found to produce products of reduced stereochemical integrity and purity. Removal of the acetonide protecting group and lactonization furnishes optically pure lactone 117 in good...
Info Pfn
Minor adjustment in oxidation level allows rapid entry to other pyrrolizidine alkaloids Scheme 124 187 . Catalytic hydrog nation of 850 gives -dihydroxyheliotridane 851 . Hydrolysis of the dithiane ring of 848 followed by exhaustive reduction of all carbonyls affords -hastanecine 853 . Reducing the carbonyl groups of 848 prior to dithiane hydrolysis allows the isolation of ester 855. Oxidation of the hydroxyl group to a ketone followed by catalytic hydrog nation of the carbonyl effectively...
Info Xnf
conditions a THF, 0 C - gt rt b CAN, H20-CH3CN c 2N H2S04 , dioxane, 70 C d HCIO4 , MeOH, H2 , Pd BaS04 e 2N H2S04 The gastric antisecretory properties of 15-deoxy-l 6-methyl-l 6-a, -hydroxyprostaglandin Ex methyl ester are associated exclusively with the 16 S diastereomer 1054. Diol 1053, a key chiral synthon for the synthesis of 1054, is readily prepared from 1031 by conversion of the primary alcohol to a tosylate, displacement of the tosylate by mixed cuprate to give 1052, and then...
Info Agp
conditions a -PrSH, CH3CN b DIBAL, CH2CI2, -78 C, 90 min c Ph3PCHCOOCH3, -78 0 - gt rt d DIBAL, 0 C, 50 min e TBS-CI, imidazole, DMF, 16 h f Zn Cu, ether, reflux 3-4 h, CI3CCOCI g Zn, HOAc, 100 C, 2-3 h 84 . An intermolecular Claisen rearrangement of 137 gives 138 with a chirality transfer of at least 98 . Attempted dehalogenation of 138 affords butyrolactone 139. -Lofexidine 143 , a weakly active a2-adrenoceptor agonist, has been synthesized in 8 steps starting from ethyl L-lactate according...
Info Mvw
conditions a excess MeMgl 93 b MEMCI, NaH 85 c MsCI, Et3N 88 d Li NH3 71 e p-TsNHN CHCOCI, DMAP, DCM 75 f Cu acac 2, dioxane 59 g Ac20, AcOH, H2S04 then NaOMe, MeOH 64 h MsCI, Et3N DMAP 74 Treatment of the diol 16 with excess trimethylsilyl chloride in acetic anhydride, an efficient acetylating agent, provides the diacetate 19 in nearly quantitative yield. This undergoes efficient pyrolysis on a large scale to generate, after subsequent reduction and hydrolysis, 3S,4S...
Ddq
-MPM deprotection with 352 -oxidative deprotection with 462, 467 Debenzylation 455 -catalytic 371, 378, 437, 438, 443 - transfer hydrogenolysis 459 S -Deltamethrin 318 Demethylation with boron trichloride 408 6-Deoxyaldehyde-L-glucose diacetonide -preparation from D-gulonolactone 383 -6-Deoxycastanospermine 435 1 -Deoxy-8,8a-di-epi-castanospermine 455 -6-Deoxy-6-fluorcastanospermine -synthesis of 435 2-Deoxy-L-galactose 343 -1 -Deoxygalactostatin 363, 364 yxo-Deoxyimino sugars -preparation of...
Info Dis
conditions a l2, Ph3P, imidazole b MVK, n-Bu3SnH, AIBN, C6H6 c Amberlyst-15, DCM d H2 Pd C, Et20 e p-TsCI, pyridine, DCM f Me2CuLi, Et20 2,2-dimethyl-l,3-dioxolane 219 in 85 yield. Subsequent Swern oxidation of 219 to the aldehyde and addition of 3,3-ethylenedioxybutyl magnesium bromide 220 provides 221. Barton-McCombie deoxygenation of the hydroxyl group in 221 followed by acidic hydrolysis of the isopropylidene ring furnishes -exo-brevicomin 87 79 Scheme 51 . Monoalkylated TosMIC 222 reacts...
HO OMOM Ywu
conditions a L-Selectride, THF, -78 C 67 b 02 gt PdCI2 CuCI2, DMF-H20 81 c H2, Pd C, MeOH 76 674b is 676 . Both are isolated from the luminescent marine polychaete Odontosyllis undecimdonta. The optical purity as determined by proton nmr is 83 ee 207 Scheme 148 . Syringolide I 681 and Syringolide 2 682 are both C-glycosides possessing a new ring system acting as specific elicitors from Pseudomonas syringae pv. tomato. Diethyl d-tartrate 2b is converted almost quantitatively to 677, which is...
Info Hca
conditions a Ph3P CHCOOCH3 b DIBAL, CH2CI2 96 c Sharpless epoxidation 92 d Red-AI, THF 98 e TBPS-CI, Et3N, DMAP, CH2CI2 89 f MsCI, THF, 0 C 100 g NaN3 , 15-crown-5, DMF, 50 C 99 h CuCI2 2H20, EtOH 87 i TsCI, pyridine, -20 C 92 In an effort to mimic the transition state of the enzymatic reduction of mevaldic acid by NADPH, nicotinamide derivative 1008 was considered a likely candidate as an HMG-CoA reductase inhibitor. Addition of -allyldiisocaranylborane to 986 provides allylic alcohol 1004 as...
Wat Is Nosyloxy Malate
0,0-Diacy ltartrimides -preparation of 443 3,3-Dialkylmalates 199 Diallyltin IV dibromide 343 3S,4R -3,5 -Diamino-2,3,5 -trideoxy- a, -pentofuranoside 163 Diazacoronands 325 DIBAL -reduction with 344, 358, 359, 375, 377, 386, 448 Dibenzoyl tartaric anhydride 430 Dibenzyl tartrate 384, 402 377 2S,3S -Di-0-benzyl-L-threitol 377 Diborane - reduction of acid with 315, 320, 407 -reduction of amide with 411 OS -1,4-Dibromo-2-butanol 218 Dibutyltin oxide 385 acid 412 Dieckmann condensation 87...
Info Tqg
- debromination 450 -decarboxylation 315 Recipavrin 62, 63 Reduction -carbonyl ketone with zinc borohydride 196, 416 -ester to aldehyde with DIBAL 386 with lithium aluminum hydride 468 with triethylsilane boron trifluoride etherate 440 -lactone to lactol 177 -of aldehyde 375 -of azide 397 -of ester with sodium borohydride 388 of halogens by hydrogenolysis 192 -of imide carbonyl 435 selective at C-4 202 -of ozonides 399 -of tosylates 327, 383, 386 -of xanthates 239, 282 -Rosenmund 431 -with BMS...
Phch2nh2 Sur Omom
conditions a PhCH2NH2 Et20 b 2 equiv. PhLi, THF, -60 C c HCI, MeOH d Boc20, toluene 63 2 steps e HI04, MeOH then NaBH4, MeOH 66 f CF3COOH, DCM g H2 PdCI2, MeOH h Boc20, toluene i p-TsCI, DMAP, DCM j NaCN, DMSO, 90 C k 2N HCI, EtOH treated with 2-lithio-2-methyl-l,3-dithiane, and hydrolyzed with mercury II chloride to provide ketone 684, where the MI protecting group undergoes loss of methoxy, resulting in simultaneous protection of the vicinal hydroxy groups as the acetonide. Hydride reduction...
Info Yox
conditions a Ph3P CHCH CH2 b DIBAL, CH2CI2 , 0 C 96 c l2 , benzene, hv d TsCI, pyridine 95 e NaCN, DMSO 99 f NaOH, MeOH g CH2N2 , ether 99 h NH2OH HCI, KOH, MeOH 96 i Nal04 , Na2S203 , H20 Oxidation of the phenyl group to an acid with ruthenium tetroxide followed by esterification with diazomethane furnishes the -citramalate 1028 with 97.2 ee. S -Citramalic acid 1029 is readily reduced to triol 1030 with either diborane 222 or borane methyl sulfide trimethylborate 223 . Conversion of 1030 to...
Info Cmg
conditions a DIBAL, toluene-hexane-78 C b Ph3P CHCOOMe, MeOH c Ph3P C Me 2 d HCI04 THF e Nal04l MeOH, pH 7.2 The lithium enolate of 4a undergoes alkylation with highly reactive electrophiles to provide pentasubstituted trans cis dioxolanes in yields ranging from 40-80 . The stability of the enolate toward allylations and benzylations but not w-alkylations can be rationalized as due to the rigid acetonide skeleton, which holds the enolate n system and the C-O o bond perpendicular to each other...