Inosamines

Selective replacement of hydroxyl groups by bromine has been reported for some inositols and inosamines. DL-2-Amino-2-deoxy-epi-inositol hydrochloride plus acetyl bromide in acetic anhydride gave, after 6 hours at 150°, DL-4-acetamido-l,2,6-tri-0-acetyl-3,5-dibromo-3,4,5-trideoxy-c/uro-inositol in 32% yield, the bromine atoms having been introduced with inversion.407 Under related conditions, DL-epi-... 

Conversion to carbamates. Cyclic carbamates derived from sugars and related compounds have repeatedly been encountered, the first being an inosamine derivative, obtained by Curtius degradation of dihydroshikimic acid.82,83... 

SG7F10.12 StsB 507 15245 NADFI Af-amidino-5cy/to-inosamine oxidoreductase... 

SG7F10.13 StsA 410 15279 L-Alanine Af-amidino-3-keto-5cy/to -inosamine AT... 

SG7F10.14C StrO 259 30135 Af-Amidino-scy/to -inosamine-4 phosphate phosphatase... 

SG7F10.16 StrB2 350 17123 scyllo -Inosamine-4-phosphate amidinotransferase... 

The General myo-lnositol and scyllo-Inosamine Pathway. Two distinct cyclitol pathways, which we earlier called Ca (started by myo-inositolphos-phate synthase) and Cb (started by T-deoxy-i cy/to-inosose synthase), are used in the initiation of AGA pathways. Here we will describe the Ca route and the Cb pathway in the paragraph on NEOs (see Section 2.2.2.1.3). The cyclitol pathway in the biosynthetic pathways for STRs, but also for other AGAs such as SPCs, KAS, and FORs and also the mixed type antibiotic HYG-A (see Section 2.2.4.3.1), starts with the formation of myo-inositol in a two-step pathway (Ca) that is not encoded in the itrAtt-clusters. The first step in streptidine biosynthesis (and any other myo-inositol utilising pathway) is the formation of a myo-inositol monophosphate (D-myo-inositol-3-phosphate or L-myo-inositol-1-phosphate) via L-myo-inositol-1-phosphate synthase, which in actinomycetes... 

Odakura et al. used a high producer derivative of M. olivasterospora MK-70 (DSM 43868), strain KYI 1250, to isolate 25 mutants blocked in at least 10 different steps of biosynthesis, as juged from complementation patterns in cosynthesis or biotransformation studies using vcy/to-inosose, cy/to-inosamine... 

Formation of the Initial Cyclitol. The first steps of FOR production are the same as in the biosynthesis of STR in short, the first step in FOR biosynthesis is postulated to be the formation of a myo-inositol monophosphate (D-myo-inositol-3-phosphate or L-myo-inositol-1-phosphate) via the cellular l-myo-inositol-1-phosphate synthase as in the STR pathway (Ca pathway see Section 2.2.1.2). As in the itr-Att-clusters, no gene for this enzyme has been found in the/or-cluster. As a second step in FOR biosynthesis the dephosphorylation of D-myo-inositol-3-phosphate via an inositolmonophosphate phosphatase has to follow. A putative gene product with this activity is that of the ForA protein (cf. Tables 2.17 and 2.18). The cyclitol is postulated to be first converted via two enzymes, a cluster-encoded myo-inositol 3-dehydrogenase (ForG member of the GFO/IDH/MocA oxidoreductase family) and the L-glutamine icy//o-3-inosose 3-aminotransferase (ketocyclitol aminotransferase I ForS), to icy//o-inosamine (3-deoxy-3-amino- cy/to-mositol). 

Since HYG-A and HYG-B are prodnced in the same strain and both contain an aminocyclitol nnit, neo-inosamine-2 and 2DOS, respectively, it is interesting to note that both pathways do not seem to share any biosynthetic steps. This becomes evident when analyzing both the resnlts of a recent biogenetic study... 

Aminocyclite (Inosamine) lassen sich selektiv oxydieren, wenn man die Aminogruppe durch geeignete Substituenten wie Carbobenzoxy- oder Acetyl-Gruppen schiitzt. 

So konnten Heyns und Paulsen N-Carbobenzoxy-D,L-myo-inosamin-4 (70) zu N-Carbobenzoxy-2-keto-D,L-myo-inosamin-4 (71) oxydieren, wo-... 

In ahnlicher Weise wird auch bei N-Acetyl-l-desoxy-myo-inosamin-4 (72a) und N-Acetyl-l-desoxy-N-methyl-myo-inosamin-4 (72b) nur die axiale Hydroxylgruppe in eine Ketogruppe iibergefiihrt 83, ss). 

Beim N-Acetyl-D,L-inosamin-l (74), das zwei axiale Hydroxyl-gruppen enthalt, wird nur die meta -standige Gruppe angegriffen... 

Interessanterweise lassen sich Tetraacetyl-desoxy-inosamine 76—79 mit nur einer freien Hydroxylgruppe nicht oxydieren, sondem man er-halt bei dem Versuch einer Oxydation das Ausgangsprodukt zuruck >. Die Ursache fiir dieses Verhalten ist nicht ersichtlich, da nur bei 76 eine bevorzugte Konformation mit freier aquatorialer Hydroxylgruppe vor-liegen sollte. 

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