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TBE RE.AO'l'IOX OT O.i..tl.DOr .. "'.i.~Jdi-\.:l'ES "i'iTrJ-I Xi~kONIA
.A ·i;hesis ;,,rt;serrtc.: in parti81 fulfilmen·~
of the degree of i lls·ce1~ of Science in O hemis trJ at
Hsssey University
David j"ohn Giltrar, l!=:69
APSTRAC'J1
A fec1ture of typical cc1rbollydra te/ a1:-rno,1ic1 reactions is the formation of complex miz-cures of imic1azoles (EJwong other products).
'rhese imidazole mixtures have proved e;ifficult to sept11·ate in many cases • .A theory for cation exchange cbromatograpr:y of bases has been developed
in this work: and applied to the separation of imidazole mixtures. The technique used appears to be capable of separatin& mixtures of imidazoles more effectively ~han other previously used.
D-Glucosone (D-arabo-hezosulose) was p:ccpered by the action of
benzaldehyde on glucosazone (d-ara bo-hexosephenylosezone) end its reection with ammonia investigated. It WE•s found that the reaction mixture
included a number of imidazoles. These imidazoles ~ere separated by
the
ion exchange technique developed eaTlicr and a totc1l of sixteen oompo\lJlds giving a positive reaction with tbe i.mida zoJ,e-specific. Pauly reagent (diazotisea sulp!wnilic acid) were detected. Fifteen of these oompounq.£1 were isolated and six we1·e ide:1tifiea by mass spectrometry and/or nucl88r magnetic resovance spectrometry.
It was also intcnrJed to investigate the reaction of 4--0-methyl-D-
gluoose and ammonia. It was proposecl to prepare this compound by methylation of rrethyl-2,3,·'+-tri-0-acetyl- -D-glucopyranoside with ,ne·thyl iodide in the presence of silver oxide. Under these conditions an acetyl migration from the 4--0 to 6-0 position occurs with tile mathylation to give
methyl-2,3,6-tri-O-acetyl•1l.-O-methyl- -D-glucopyranoside which may be hydrolysed to give 4--0-methyl.-D-glucose. It was intended to t;repare the starting mate:cial for this reaction (methyl-2, 3, 4.-tri-O-acetyl.- '. -D- glucopyranoside) from D-glucose by 'i:;be following steps.
(1) ketJi<lnolysis of D-·3lucose catalysed by an h.+ cation exchange resin to give methyl- :· -D-glucopyrunoside.
(2) Blocking of the 6-0 position with triphenylchloromethane.
(3) Acetylation with acetic anbyo.ride to 2;ive r,1ethyl-6-0-triphenylmethyl- 2, 3, 4--tri-O-acetyl- . -D-glucopyranoside.
(4) 3emoval of the triphenylmethyl blocking group to give the required methyl-2, 3, 11.-tri-0-acetyl-
\·!,
D-:~lucopyranoside.In fact at the time of this writing the first three steps lwd been accomplished but attempts to remove the k iphenylroothyl blocking group while l eavinr, the ocetyl g:coups intact hac1 proved unsuccessful.
for encoura:_,:,.r.,.::nt anc! advice.
(1) (2)
r;::; BLE OF CONmiJTI~S
----.. .
- ____ _ _ __
..,_ __
....X3STlh GI'
J.lkaline Degrada-:;ion of Sugars
Fo:cI!l8tion of rj -Desoxyosones :Reactions of the DesoxJosones Alk8line Pission
S8ccharinic ~wid Foruwtiol1 The Effect of :::iuostitut ion
(1) ifon-:..:-c:C:ucing hexoses
(2) 1-0-sl,bstitntecJ. 2-keto~1exoses
(3) 2-0-substitute(::i aJ.,:lohexnses ( 4) 3-0-substUutecJ hex'.Jses (5) 4--·0-su bst Uute
a
hexosc.::;(6) 6-0-subctitut'"',:; hc::os•Js
Formation of .ffat erocyclic Comi!OLL"tds ( 1) Irnioa zolcs
i i
1.
1 3
3 3 3 7
7 7 7
7 8 8 8 8
(2) Other Eeterocyclic compouncs 12
rheory of Ion-Bxchan._: _ _-, Sc:i.'1:cat ion of Bases Criteris for s~parat i-:,n
Separation of c1n Lnidc1zolc ~.:ixbn'E:
Chro, 1atography
D-a:::'8 bo-hexosephen._vl osa zon3 D-arabo-hexosulose (D--C0h,co:::::-vi~) Separation of IrnidazoJ.es
D-Glucosone/_.'.,.mi11onia ~eaction
Kinetic Study
Preparative Reaction
Ion r::~~chenr;e separat ion of lws(;s
16 19 23 24
26 27 27 23 30 32 32 32 35
:':tesults
Cornp0t:.nd I Compound IV Compo•'.rd VI Compound
XI
Compounc XII Compound XIII Cor.1pounc. X:J
RESUL'.i'S A!',D DI5Cu!:i.S::::0N
(von -, t ent,SJ .L \
Compound I 2,
4.(?,,
5 )-bis ( ·cc trc1 hyC.roxybt..:~yl) iri,ida zole Compound IVCompound VI \( 5)-te·~ra hyo1•cxybutyli:c1ida zol(::
Co;·,,pou;v,3 ]~II 4-( 5 )--( 2--lrycl:rox:\:etb.,,_vl) i1aioa zole and XIII 2-hyd"'.'OX}:i:et byl-~.( 5 )-inetb.yli;,1ida zole Compoun-.:l 'JJT 1:.( 5) -in::; -c hy 1 imir~a zo~.1:;
D-Glucosone/;\m1nonia :::t~'3 c·~io:1
SEC•"7'I0_ _, 11:r II I + -0-~_ . "<'·..J.:J 1·1
.-'!".
-·~·.w ."
_n...J _\zr•TF,,..,N'_J_, J\..,\.) .. '~/.t'-.\i .J. --,:01·1 '' 'i •i.Exper imenta 1
i1~ethyl- .. D-Glucopyra,-i_osiC:e
] ~ethyl-6-0-tripl1,:;112rl-in0t t-:rJ.-2, 3, 1:---t:ci--0-ac0tyl--
(3
-D-39 39 39
l:D
42
/.i.7 51
glucopyranoside 54.
FIGUEf.S
:B'ig. :L Lobr_y c!.e Bruyn-Albe::cda Var. Ekens·cein .i.1;:;actions Fig.2 l'.echanisin of tho J.ldol Condens8tion
Fig.3 Isomeris&tiLm by tl1e alaol Concler.sE:tiou J.i'ig. It-
(3
-}i;lirninat ion :,~echanismFiJ;. 5 ;,lkal ine Fission of }Jic;:,:,:>bo.-1_yls
Fig. 6 Saccha:cinic :,cic-: Fo:::'u1at ion fror:1 f _-Desoxyosones
2
4-
5 6 9
Fi&.,. 7 'I'ha :Sffect oi' Substit-.xi~io11 on Desoxyosone Fo1:m&tion 10 Fig. 3 Fo1"'i.i.:ition of liete.i.·ocycl ic Coopounds 13
Fig. 9 Prepa:r.8t ion of D-C-lucosonG 25
.F'i.s. 10 Developmcn-i; of L.1ida zole Conuentrc:, tio,1 v-;i ~h 'i'ime in G-lucosone/1.rnVionia 1foaction
I<1ig. :!..1 1•.:as::: Spectra of Ic:ientifiec: ImiJa zoles
Ar,.nonfa S~rstem
li"ig.13 Fort,1·::-ition of Iuida zolcs f:2om lJ-Glucosonc~
Fig;.1l:. Degradat i on of 3.r •? .. ,:::t hyl-D-ca,_-._cose
Fig.15 11.-0--L:cthy:!.£Jt ion of l .r::thyl-2,3,1:.-tri-0-acetyl- slucopyranoside
'l'sble I 2.esuJts of Sepa:rnt:.c~·- of Im;.f.!,,,z.olc Lixture
D-
Table II Spots l0catec1 by i-\::ipcr Ch:::-owitogrsphy of G·lucosone/
Table III Compounds in frac·i:;ions frorri Ion--Exclwnge
3) + 45, l:.6
49 52
53
31
31:.
Ch:::-0111.9tography 37
;Cable IV CompouncJ.s Isola-tea fi•om Glucosone/Airr.0.nnia Reaction 38
